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Nucleic acid sequence analysis software packages.

Software packages have made sequence analysis easier and more accessible to research scientists in many fields. The majority of these packages are routinely upgraded to include improved and innovative programs for primer design, sequence assembly and improvements in database searching programs. The interfaces of many packages have also been improved, greatly facilitating their use. In the future, researchers can expect to be able to access a growing number of network applications (e.g. database searching and exon prediction programs) from within software packages, making them accessible in familiar formats. Increased network access from within software packages will also make more databases, and more frequently updated databases, available to a larger research community.

Base Sequence↗

Comparative metagenomic assessment of Illumina-compatible library preparation methods, short-read lengths, and PacBio HiFi sequencing reveals differences in microbial and functional diversity recovery from a complex environmental sample.

UNLABELLED: Metagenomics enables comprehensive exploration of microbial communities but is influenced by library preparation and sequencing technologies, affecting recovery of microbial genomes and proteins. Here, we benchmarked six Illumina-compatible short-read library preparation conditions in triplicate at 2 × 150 bp and 2 × 250 bp read lengths alongside PacBio HiFi long-read sequencing using a composite environmental sample of marine mangrove sediment and terrestrial palm tree soil. Longer short reads (2 × 250 bp) combined with optimal library preparation approaches improved assembly quality, protein detection, and metagenome-assembled genome (MAG) recovery, achieving results approaching those of long-read sequencing. TruSeq libraries at 2 × 250 bp recovered more than sevenfold more unique proteins than the same kit at 2 × 150 bp (811,701 vs 110,108) using the same number of sequencing reads, while recovering a comparable number of high-quality MAGs to PacBio HiFi long-read sequencing (11 vs 18) and surpassing it in protein discovery by almost 10-fold (811,701 vs 87,745) at less than half of the sequencing cost. Furthermore, biosynthetic gene cluster analysis identified 46 biosynthetic gene clusters in TruSeq-250PE assemblies compared to 38 in PacBio HiFi, with several showing no close match in the MIBiG database. Although long reads yield more contiguity and complete genomes, longer short reads offer a cost-effective, scalable alternative for uncovering microbial and functional diversity. These findings provide critical guidance for metagenomic experimental design, demonstrating that strategic selection of library preparation chemistry and sequencing parameters can reveal more unknown microbial information in complex biomes without requiring additional sequencing depth. IMPORTANCE: Metagenomic outcomes are strongly influenced by library preparation and sequencing strategies, yet their combined effects in complex environmental samples remain poorly defined. Here, we provide the first direct comparison of Illumina NovaSeq short-read metagenomic sequencing at 2 × 150 bp and 2 × 250 bp across multiple library preparation kits, alongside PacBio HiFi long-read sequencing. We show that sequencing read length and library preparation critically shape assembly quality, protein recovery, and metagenome-assembled genome (MAG) reconstruction. These findings demonstrate that short-read sequencing at 2 × 250 bp, with appropriate library preparation, can match long-read technologies in MAG recovery while substantially surpassing them in protein discovery. With less than half of the sequencing price and a 3.5-fold reduction in cost per gigabase of usable data, this method facilitates more accessible large-scale metagenomic analysis within complex environmental systems.

Metagenomics↗

Volunteerism by students at risk.

This program has made it possible for students to experience some important firsts: the first report card they are proud to share, the first award they receive at an honors assembly. Students have gained a new awareness of the elderly: "I never used to look up to them," one student said. "Now I really understand that they are history. I will have more respect for the elderly, because I will want respect when I am older."

Adolescent↗

Amplicon and metagenomic sequencing reveal thifluzamide drive rhizosphere microbial structural shifts and functional adaption.

Thifluzamide (TF) is a widely used phenyl urea fungicide in rice production; however, its impacts on the structural composition and functional dynamics of the rhizosphere microbiome remain poorly understood. Here, we systematically investigated the effects of TF on the structure, interactions, and functional potential of the rice (Oryza sativa L.) rhizosphere microbiome using integrated amplicon sequencing and metagenomic approaches. TF application significantly altered both bacterial and fungal community composition, bacterial diversity was markedly reduced, whereas fungal diversity increased. With bacterial diversity markedly reduced while fungal diversity increased. Beta-diversity analyses revealed strong treatment-driven community separation, indicating pronounced TF-induced microbial restructuring. Co-occurrence network analysis demonstrated reduced complexity and connectivity in bacterial networks but increased negative co-occurrence patterns within fungal communities, suggesting contrasting stability responses between microbial kingdoms. Metagenomic profiling further revealed substantial functional shifts, including the differential enrichment of KEGG and COG pathways associated with xenobiotic metabolism. Notably, while total ARG abundance remained stable, TF exposure altered the resistome profile by selectively enriching specific classes of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and mobile genetic elements (MGEs). Strong positive correlations between MGEs and ARGs highlighted an elevated potential for horizontal gene transfer. Metagenome-assembled genome (MAG) analysis identified specific TF-enriched bacterial taxa, including Methylophilus, Sulfurospirillum, and Azospirillum, which harbored genes involved in pesticide degradation and xenobiotic transformation. Collectively, these findings demonstrate that TF profoundly reshapes the rice rhizosphere microbiome by altering microbial diversity, interaction networks, resistance gene profiles, and functional capacities. This study provides genomic insights into fungicide-microbiome interactions, underscoring the potential ecological implications associated with TF application, while identifying candidate microbial taxa that may contribute to pesticide degradation and rhizosphere microecology resilience.

Rhizosphere↗

Reframing Balint: thoughts on family medicine departmental Balint groups.

This paper explores recurrent processes and themes in the 1,300 family medicine faculty, resident, intern, and community Balint groups the author has facilitated/led. The frequent group "deviation" from the central Balint task of understanding difficult physician-patient relationships is reframed as less "resistance" or "obstacle" to work, as it is an expression of unmet developmental needs and organizational realities. When group members are carefully attended to (by facilitator and one another), the group often becomes emotionally capable of addressing a "case " in the conventional Balint understanding of the work the group has assembled to do. The group dynamics of such "hybrid" Balint groups thus become comprehensible as other than error.

Family Practice↗

Life history trade-offs assemble ecological guilds.

Ecological theory predicts that competition for a limiting resource will lead to the exclusion of species unless the within-species effects outweigh the between-species effects. Understanding how multiple competitors might coexist on a single resource has focused on the prescriptive formalism of a necessary niche width and limiting similarity. Here, we show how continuously varying life histories and trade-offs in these characteristics can allow multiple competitors to coexist, and we reveal how limiting similarity emerges and is shaped by the ecological and evolutionary characteristics of competitors. In this way, we illustrate how the interplay of ecological and evolutionary processes acts to shape ecological communities in a unique way. This leads us to argue that evolutionary processes (life-history trait trade-offs) are fundamental to the understanding of the structure of ecological communities.

Animals↗

Virus-mediated fate of antimicrobial resistance genes in livestock manure anaerobic digestion.

Antimicrobial resistance (AMR) poses a critical global health challenge, with livestock manure acting as a significant environmental reservoir for antimicrobial resistance genes (ARGs). Anaerobic digestion (AD) is a pivotal process for mitigating ARG dissemination at the livestock-environment-human interface. This study aims to elucidate the global dynamics of ARGs in AD systems, focusing on virus-host interactions and arms race, to identify actionable strategies for AMR control. We analyzed 205 metagenomic (4.5 Tb) and 36 meta-transcriptomic (640 Gb) datasets, including 15 newly generated datasets, revealing that pig manure AD harbors the highest ARG abundance (0.668 ARGs/16S rRNA), while AD systems generally exhibit limited transcriptional activation of ARGs. We constructed a viral dataset for livestock manure AD (GVD_LMAD), comprising 59,316 DNA and 727 RNA viral operational taxonomic units (vOTUs). Virus-host interactions established by CRISPR-Cas spacer, tRNA and homology matches revealed 889 lytic infections of antimicrobial-resistant bacteria (ARB) compared to only 18 ARG transduction events. Further analysis showed that the relative abundance of vOTUs assigned to the reduction role (4.11% ± 3.19%) was substantially higher than that of reproduction (0.72% ± 0.64%) and transduction (0.19% ± 0.30%), demonstrating that, among viral processes, lysis outweighs transduction in contributing to ARG abundance reduction in AD. Furthermore, an antiviral defense system (ADS) catalogue (GADSC_LMAD), derived from 2760 high-quality metagenome-assembled genomes (MAGs) containing 39,307 ADS, with ADS prevalence in ARB (7.8 ± 6.0 per MAG), indicating an intensified virus-host arms race in AD that may shield ARB from phage lysis. The resulting CRISPR-Cas immune network with expressed spacers targets foreign ARG-carrying sequences (primarily plasmids and ICEs), suggesting a mechanism that restricts horizontal gene transfer (HGT) via conjugation and transformation, despite shielding ARB from phage lysis. Collectively, these findings highlight that viral communities significantly contribute to ARG reduction through phage lysis relative to transduction, while the ADS-mediated arms race, despite protecting ARB, constructs a biological firewall that potentially limits HGT of ARGs. This study provides novel insights into virus-host dynamics as a key mechanism for controlling ARG dissemination in AD systems.

Animals↗

Health and welfare administration system in Japan.

The health and welfare administration system in Japan is based on the concept of "welfare nation" in the Constitution, and the Ministry of Health and Welfare has prime responsibility for general health and welfare administration. There are two levels of the prefectural governments and municipal governments with their own assemblies. The health centers and the welfare offices are special and first-line organizations for the health and welfare administration, and they are operated by the prefectures or large municipalities in principle. This system has now been experiencing the reform adapted to the aging of population, based on the amendment to the Health Service for the Aged Law and so on in 1990 and the amendment to the Health Center Law in 1994, which is now the Community Health Law. The municipal government is becoming a first-line organization for the health and welfare administration and its responsibility is growing especially in the personal service for the residents.

Health Services Administration↗

Characterization of viral proteins encoded by the SARS-coronavirus genome.

A new disease, termed severe acute respiratory syndrome (SARS), emerged at the end of 2002 and caused profound disturbances in over 30 countries worldwide in 2003. A novel coronavirus was identified as the aetiological agent of SARS and the 30kb viral genome was deciphered with unprecedented speed in a coordinated manner by the global community. Since then, much progress has been made in the virological and molecular characterization of the proteins encoded by SARS-coronavirus (SARS-CoV) genome, which contains 14 potential open reading frames (ORFs). These investigations can be broadly classified into three groups: (a) studies on the replicase 1a/1b gene products which are important for viral replication, (b) studies on the structural proteins, spike, nucleocapsid, membrane and envelope, which have homologues in all coronaviruses, and are important for viral assembly and (c) expression and functional studies of the "accessory" proteins that are specifically encoded by SARS-CoV. A comparison of the properties of these three groups of SARS-CoV proteins with the knowledge that coronavirologists have generated over more than 30 years of research can help us in the prevention and treatment of SARS in the event of the re-emergence of this new infectious disease.

Genome, Viral↗

Does 'errorless learning' compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia?

BACKGROUND: Because neurocognitive impairments of schizophrenia appear to be 'rate limiting' in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia. METHOD: The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-tank assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizoaffective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training. RESULTS: For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment. CONCLUSIONS: These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia.

Adult↗

Smoking policy and cessation in an inner-city hospital.

Hospital policies regarding cigarette smoking can affect the smoking habits of employees, patients, and visitors. Successful smoking policy development and impact have been reported in a number of hospitals. These reports have been from financially secure or university hospitals. This article reports on the policy experience at Interfaith Medical Center, a public hospital serving an economically disadvantaged black inner-city community. Policy implementation and smoking cessation efforts were directed by a broad-based hospital committee. An employee survey demonstrated support for a policy restricting but not banning smoking (89% of nonsmokers, and 80.2% of smokers). Among smoking employees, 87.6% wanted to quit. A policy restricting smoking to designated areas in the cafeteria and coffee shop was enacted. Health fairs and smokeout contests were enthusiastically received and resulted in short-term cessation verified by exhaled carbon monoxide levels. Assemblies where ex-smokers were given "Hall of Fame" certificates, "stop smoking" art contests, and a "stop smoking hotline" generated further cessation activity. The department of medicine, in cooperation with the National Heart, Lung, and Blood Institute's Smoking Education Program, set up a training program for residents on how to help patients quit. Overall, the smoking prevalence, attitudes, and enthusiasm to quit were similar to previous reports in financially secure hospitals. Unfortunately, lack of resources and staff turnover led to dissolution of the program. Institutional stability and a funding source are critical for the long-term success of hospital smoking cessation programs.

Adult↗

Results of the ACSUS for pediatric AIDS patients: utilization of services, functional status, and social severity.

OBJECTIVE: This study describes demographic characteristics of pediatric AIDS patients, describes hospital and community-based service utilization patterns, and analyzes medical and social support service usage patterns with respect to patient demographic characteristics, clinical trial participation, functional/developmental status, and social environment. DATA SOURCES AND STUDY SETTING: Data reported in this study are from the AIDS Costs and Service Utilization Survey (ACSUS) and cover the six-month period beginning March 1991 (N = 135). Pediatric patients who sought care for HIV-related problems were sampled at seven different hospitals in five metropolitan regions of the United States. All of the participating hospitals had clinics specifically serving pediatric patients infected with HIV. The sample consists of HIV-positive patients who had had at least one HIV-related symptom or condition. STUDY DESIGN: A stratified probability sample design guided the sampling strategy, which included oversampling in two large hospitals from two of the five metropolitan areas. Survey data cover an 18-month time period of health care utilization, cost, and financing information from HIV-infected patients and their providers. Utilization measures are standardized to a six-month period. Per capita income, family structure, informal personal network, functional status, and clinical trial participation are tested for associations with patterns of utilization. In addition, a weighted ten-point social severity scale was developed to assess family/household stability. DATA COLLECTION: Data were collected through a screener instrument completed by the person accompanying the child to a hospital clinic visit (usually a a parent), and through two interviews conducted in person with the patients' primary caregivers. Data from the questionnaires were coded and assembled into computerized SAS analysis files by WESTAT: PRINCIPAL FINDINGS: Children in this sample are 62 percent African American, 25 percent Hispanic, and 10 percent White. Medicaid is the primary payer for 92 percent. Mean per capita income is $3,440. Fewer than one-half (41 percent) of the families of the children receive Aid to Families with Dependent Children (AFDC). (AFDC). Within the six-month period, approximately one-third of the sample (29.6 percent) was hospitalized. Mean length of stay was 16.0 days. Clinical trial participation was positively related to mean number of hospital clinic visits and receipt of formal (paid) home care. There were no differences in use of community clinic, mental health, and inpatient facilities by clinical trial status. Participation in clinical trials was positively related to income and negatively related to social severity. In four cities, emergency room use was consistently lower for clinical trial participants than for nonparticipants. CONCLUSIONS: Data from the first six months of the ACSUS pediatric sample suggest that participation in clinical trials may bring about access to social services that appear to reduce emergency room use. However, the findings reported here are descriptive and exploratory. Further multivariate, nonparametric analyses of the full 18-month provider-patient merged data set are necessary to confirm the simple correlations found in this study.

Acquired Immunodeficiency Syndrome↗

Organisation and cost-effectiveness of antenatal haemoglobinopathy screening and follow up in a community-based programme.

OBJECTIVE: To consider the organisation cost and effectiveness, of universal, community-based antenatal screening for the haemoglobinopathies, and to estimate the cost-effectiveness of programmes at different levels of prevalence and mix of haemoglobinopathy traits. DESIGN: Retrospective review of laboratory and Sickle Cell and Thalassaemia Centre worksheets with costing of capital equipment, consumables, salaries and overheads, and estimation of costs in a range of circumstances. SETTING: A haematology department, including a Sickle Cell and Thalassaemia Centre, providing antenatal and neonatal screening programmes in Inner London. PARTICIPANTS: Two thousand one hundred and one women booking at the antenatal clinic whose samples were referred for screening during 1994. MAIN OUTCOME MEASURES AND RESULTS: In addition to assessing the cost-effectiveness of antenatal haemoglobinopathy screening in a number of settings, the following specific financial information was assembled for the service in Brent: 1. cost of identifying abnormal haemoglobin in mother (ł209); 2. cost of identifying at-risk fetus before confirmation by prenatal diagnosis (ł2,455); 3. cost of providing genetic information and counselling to mother with abnormal haemoglobin (ł109); 4. programme savings from cases averted (ł61,000). Conclusions Antenatal screening with follow up counselling can be self-financing at most prevalences of haemoglobinopathy traits, with greater savings where a high proportion of the traits are beta thalassaemia. There is a net financial cost (ł1,350) only at prevalences below 2.5% of traits if these are mainly for sickle cell disease. Since there are other benefits is it likely that antenatal screening will be considered cost-effective even at quite low levels of trait prevalence.

Algorithms↗

CASH 2021: commercial access and space habitation.

Issues about commercialization of space have been a growing concern in the past decade for the space community. This paper focuses on the work from a team of 51 students attending the Summer Session Program of the International Space University in Bremen, Germany. CASH 2021 (Commercial Access and Space Habitation) documents a plan that identifies commercial opportunities for space utilization that will extend human presence in space, and will chart the way forward for the next 20 years. The group selected four commercial sectors that show the most promise for the future: tourism, entertainment, space system service, assembly and debris removal, and research and development/production. The content of this document presents the results of their research. Historical activities in each of the commercial sectors are reviewed along with the current market situation. To provide a coherent background for future commercialization possibilities a scenario has been developed. This scenario includes a postulated upon ideal future and includes social, political and economic factors that may affect the space industry over the timeline of the study. The study also presents a roadmap, within the limited optimistic scenario developed, for the successful commercialization of space leading to future human presence in space. A broad range of commercially viable opportunities, not only within the current limits of the International Space Station, but also among the many new developments that are expected by 2021 are discussed.

Agriculture↗

The role of immigrants in the assembly of the South American rainforest tree flora.

The Amazon lowland rainforest flora is conventionally viewed as comprising lineages that evolved in biogeographic isolation after the split of west Gondwana (ca. 100 Myr ago). Recent molecular phylogenies, however, identify immigrant lineages that arrived in South America during its period of oceanic isolation (ca. 100-3 Myr ago). Long-distance sweepstakes dispersal across oceans played an important and possibly predominant role. Stepping-stone migration from Africa and North America through hypothesized Late Cretaceous and Tertiary island chains may have facilitated immigration. An analysis of inventory plot data suggests that immigrant lineages comprise ca. 20% of both the species and individuals of an Amazon tree community in Ecuador. This is more than an order of magnitude higher than previous estimates. We also present data on the community-level similarity between South American and palaeotropical rainforests, and suggest that most taxonomic similarity derives from trans-oceanic dispersal, rather than a shared Gondwanan history.

Biological Evolution↗

Antivirals for the common cold.

BACKGROUND: The common cold is a ubiquitous short and usually mild illness for which preventive and treatment interventions have been under development since the mid-40s. As our understanding of the disease has increased, more experimental antivirals have been developed. This review attempts to draw together experimental evidence of the effects of these compounds. OBJECTIVES: To identify, assemble, evaluate and (if possible) synthesise the results of published and unpublished randomised controlled trials of the effects of antivirals to prevent or minimise the impact of the common cold. SEARCH STRATEGY: We searched electronic databases, corresponded with researchers and handsearched the archives of the MRC's Common Cold Unit (CCU). SELECTION CRITERIA: We included original reports of randomised and quasi-randomised trials assessing the effects of antivirals on volunteers artificially infected and in individuals exposed to colds in the community. DATA COLLECTION AND ANALYSIS: We included 241 studies assessing the effects of Interferons, interferon-inducers and other antivirals on experimental and naturally occurring common colds, contained in 230 reports. We structured our comparisons by experimental or community setting. MAIN RESULTS: Although intranasal interferons have high preventive efficacy against experimental colds (protective efficacy 46%, 37% to 54%) and to a lesser extent against natural colds (protective efficacy 24%, 21% to 27%) and are also significantly more effective than placebo in attenuating the course of experimental colds (WMD 15.90, 13.42 to 18.38), their safety profile makes compliance with their use difficult. For example, prolonged prevention of community colds with interferons causes blood-tinged nasal discharge (OR 4.52, 3.78 to 5.41). Dipyridamole (protective efficacy against natural colds 49%, 30% to 62%), ICI 130, 685 (protective efficacy against experimental colds 58%, 35% to 74% ), Impulsin (palmitate) (protective efficacy against natural colds 44%, CI 35% to 52% ) and Pleconaril (protective efficacy against experimental colds 71%, 15% to 90% ) appear to have important antiviral properties and are well-tolerated. The evidence of effectiveness of other compounds in the treatment of experimental or natural colds is sparse. REVIEWER'S CONCLUSIONS: There are no licensed effective antivirals for the common cold. Because prolonged intranasal administration causes a clinical picture which is not distinguishable from the common cold, interferons have no place in everyday use. Further assessment of the effects of dipyridamole, palmitate, ICI 130, 685, Impulsin and Pleconaril in preventing the common cold should be carried out. Given the multi-agent nature of the causes of the common cold, future research efforts should focus on non virus-specific compounds.

Administration, Intranasal↗

Assessing the effect of psychiatric disorders on work function.

In summary, an effort to increase the specificity and replicability of assessments of disability has been made by a subcommittee on permanent psychiatric disability, consisting of four forensic psychiatrists, three clinical and forensic psychologists, a medical sociologist, a workers' compensation judge and a vocational rehabilitation expert. The subcommittee reviewed legislation, regulations and case law pertaining to workers' compensation, especially that related to compensation for work-related psychiatric injury in California. The subcommittee also reviewed published and unpublished papers that discuss problems related to the evaluation of claims arising from alleged work-related psychiatric injury in the California Workers' Compensation System. A limited review of existing systems for evaluating psychiatric disorder and psychiatric disability was carried out. A number of consultants, psychiatrists and psychologists reviewed the work independently or attended meetings at which the work was presented. Out of this work, a report was generated that has been described in detail in this chapter. An outline for assembling all of the data necessary for arriving at conclusions about impairment of work functions was generated. Eight work functions were chosen, derived from Social Security disability guidelines but somewhat modified to fit the issue of partial disability. Specific component factors for each of these work functions were identified. It is hoped that this method will provide a more quantitative, replicable and equitable system for assessing permanent psychiatric disability. If these are applied in good conscience by the medical-legal community, data will be generated that will make it possible to further modify specifications of these work functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Leukemia incidence by occupation in the Portland-Vancouver metropolitan area.

During a 15-year period in an urban area with over a million inhabitants, we identified 1,678 cases of leukemia among residents aged 16 or older. Case finding was done according to the methods of the National Cancer Institute (NCI) SEER program. Usual occupation was coded by a system based on the U.S. Census Bureau classification. According to age-standardized incidence rates for persons aged 16-67, significant excess leukemia risks were found for 14 male and 8 female occupation categories, with the larger number of male excess risk situations due to nonlymphatic leukemia. Lymphatic leukemia risks were significantly elevated among dentists, school teachers of both sexes, auto mechanics, gas station attendants, female assembly workers, and female laundry and dry cleaning workers. Nonlymphatic leukemia risks were significantly elevated among machinists, other metal tradesmen, heavy equipment operators, textile operatives, meat cutters, cannery workers, construction laborers, freight and stock handlers, policemen, and firemen. Risks of both types of leukemia were significantly elevated among registered and practical nurses and lumber mill workers. This study has not identified specific etiologic agents and exposures, but applied investigations aimed at disease control by prevention of cases are now possible in this community. Nationwide surveillance and control are recommended.

Adolescent↗