bluuebunny/crossref_metadata_2025 huggingface dataset:
The Community-Based Health Workforce in Public Health and Health Care Delivery
Authors: Ahmed Kaha , Presley-Cantrell Letitia , Moeti Refilwe , Wong David , Freese Kimberly L. , Taplin Caroline , Rodrigue Jacqueline , Spencer Tara D. , Hacker Karen
Published: July 2024

Context:

The “community-based workforce” is an umbrella term used by a workgroup of U.S. Department of Health and Human Services (HHS) leaders to characterize a variety of job titles and descriptions for positions in the public health, health care delivery, and human service sectors across local communities.

Approach:

Definitions, expectations of the scope of work, and funding opportunities for this workforce vary. To address some of these challenges, a workgroup of HHS agencies met to define the roles of this workforce and identify existing opportunities for training, career advancement, and compensation.

Discussion:

The community-based workforce has demonstrated success in improving poor health outcomes and addressing the social determinants of health for decades. However, descriptions of this workforce, expectations of their roles, and funding opportunities vary. The HHS workgroup identified that comprehensive approaches are needed within HHS and via public health sectors to meet these challenges and opportunities.

Conclusion:

Using the common term “community-based workforce” across HHS can encourage alignment and collaboration. As the environment for this public health and health care community-based workforce shifts, it will be important to understand the value and opportunities available to ensure long-term sustainability for this workforce to continue to advance health equity.
Pivoting From Influenza to COVID-19 Vaccinations: How a Minnesota Vaccination Program Reduced Barriers for Refugee, Immigrant, and Migrant Communities Accessing Vaccines During the COVID-19 Pandemic
Authors: Johansen Ingrid , Selim Mohammed , J. Hoffman Sarah , Dawson-Hahn Elizabeth , Yu Kimberly
Published: July 2024

The Minnesota Immunization Networking Initiative (MINI) led by Fairview Health Services has addressed barriers to accessing immunizations through partnerships with community organizations to provide free influenza vaccinations to historically underserved communities, especially refugee, immigrant, and migrant communities. Once the COVID-19 vaccine was available, MINI quickly pivoted operations to distribute the vaccine and provide technical assistance to community partners amidst rapidly evolving guidance. With infrastructure and a vaccination team in place, MINI responded to new and emerging needs, eg, implementing a more accessible and low-tech scheduling system, increasing staffing to meet growing needs, and expanding partnerships with community organizations and leaders. From February 2021 to September 2023, MINI organized 1120 community-based vaccine clinics and administered 43,123 COVID-19 vaccinations. Of those vaccine recipients, 88% identified as Black, Indigenous, and other people of color, and for preferred language, over half stated that they preferred a language other than English. These demographics are similar to those of the earlier influenza clinics, even as average annual clinics have tripled and average total vaccinations have quadrupled since the pivot to COVID-19 vaccination clinics. Some keys to success were: (1) consistent, bidirectional communication and shared decision-making with community partners; (2) prioritizing sustainable staffing models with the support of administrative leadership and resources; and (3) having a community-informed approach supported by the practice of hiring staff from communities served. Because of the effectiveness of this model, MINI is primed to respond to planned and unplanned emergent public health crises.
Evaluating the Effectiveness of a Patient-Centered, Nonphysician Led Self-Monitoring Blood Pressure Program in a Rural Federally Qualified Health Center
Authors: Sanchez Magali , Hara-Hubbard KeliAnne K. , Baquero Bárbara
Published: July 2024

Context:

Uncontrolled hypertension can lead to an increased risk of cardiovascular disease, myocardial infarction, stroke, or death. Self-monitoring blood pressure (SMBP) programs have been associated with blood pressure (BP) reduction, particularly among rural, minority, and low-income individuals. There is limited literature about nonphysician SMBP programs.

Objectives:

To evaluate the effectiveness of an SMBP program designed to engage nonphysician team members in hypertension management within a federally qualified health center (FQHC).

Design:

Self-monitoring blood pressure program activities were implemented using a Plan, Do, Study, Act model. The University of Washington Health Promotion Research Center evaluated processes and patient-level outcomes in a mixed-methods design. Quantitative analysis examined clinical outcomes related to hypertension, and qualitative analysis relied on interviews with clinical staff examining program implementation, adoption, and sustainability.

Setting:

Family Health Centers (FHCs), a FQHC located in rural Washington, serving medically underserved populations.

Participants:

Two hundred five active SMBP patients out of 2600 adult patients (over 18 years old) who had a diagnosis of hypertension within the last 12 months.

Intervention:

Patients with uncontrolled hypertension were given a BP cuff to log their daily BP. Patients met with community health workers (CHWs) and medical staff to review logs and set self-management goals over 3 to 4 months.

Main Outcome Measure:

Controlled BP measurements and factors to implementation and sustainment.

Results:

Facilitators to implementation included expanded telehealth reimbursement during the COVID-19 pandemic, integration of CHWs, and linguistically adapted resources. Barriers included a lack of reimbursement for nonphysician time and BP monitors. Quantitative results demonstrated an effort to reach minoritized populations but did not show an improvement in BP outcomes.

Conclusions:

Family Health Center implemented an SMBP program adapted to meet the linguistic and social needs of their patients. The successful integration of CHWs and the need for reimbursement policies to support SMBP programs were key factors for implementation and sustainability.
Challenges of EHR “Meaningful Use” in Rural Health Centers
Authors: Brightharp Courtney , Myers Kristian , Mandelbaum Jennifer
Published: July 2024

The Centers for Disease Control and Prevention (CDC) continues to promote the utilization of electronic health records (EHRs) to support population health management and reduce disparities. However, access to EHRs with capabilities to disaggregate data or generate digital dashboards is not always readily available in rural areas. With funding from CDC’s DP-18-1815, the Division of Diabetes and Heart Disease Management (Division) at the South Carolina Department of Health and Environmental Control designed a quality improvement initiative to reduce health disparities for people with hypertension and high blood cholesterol in rural areas. With support from a nonprofit partner, the Division used qualitative evaluation methods to evaluate the extent to which practices were able to disaggregate data and report quality measures.
The Impact of Health Equity-Informed Eligibility Criteria to Increase the Delivery of Pharmacist-Delivered Comprehensive Medication Management Services for Patients with High Blood Pressure
Authors: Zagel Alicia L. , Brummel Amanda R. , Chacon Megan , O’Donnell R. May , Styles Emily , Peacock James M.
Published: July 2024

Objective:

Evaluate a cardiovascular care intervention intended to increase access to comprehensive medication management (CMM) pharmacy care and improve vascular health goals among socially disadvantaged patients.

Design:

Retrospective electronic health records-based evaluation.

Setting:

Thirteen health care clinics serving socially vulnerable neighborhoods within a large health system.

Participants:

Hypertensive and hyperlipidemic adult patients.

Intervention:

CMM pharmacists increased recruitment among patients who met clinical criteria in clinics serving more diverse and socially vulnerable communities. CMM pharmacists partnered with patients to work toward meeting health goals through medication management and lifestyle modification.

Main Outcome Measures:

Changes in the engagement of socially disadvantaged patients between preintervention and intervention time periods; vascular health goals (ie, controlled blood pressure, appropriate statin and aspirin therapies, and tobacco nonuse); and the use of health system resources by CMM care group.

Results:

The intervention indicated an overall shift in sociodemographics among patients receiving CMM care (fewer non-Hispanic Whites: N = 1988, 55.81% vs N = 2264, 59.97%, P < .001; greater place-based social vulnerability: N = 1354, 38.01% vs N = 1309, 34.68%, P = .03; more patients requiring interpreters: N = 776, 21.79% vs N = 698, 18.49%, P < .001) compared to the preintervention period. Among patients meeting intervention criteria, those who partnered with CMM pharmacists (N = 439) were more likely to connect with system resources (social work: N = 47, 10.71% vs 163, 3.74%, P < .001; medical specialists: N = 249, 56.72% vs N = 1989, 45.66%; P < .001) compared to those without CMM care (N = 4356). Intervention patients who partnered with CMM pharmacists were also more likely to meet blood pressure (N = 357, 81.32% vs N = 3317, 76.15%, P < .001) and statin goals (N = 397, 90.43% vs N = 3509, 80.56%, P < .001) compared to non-CMM patients.

Conclusions:

The demographics of patients receiving CMM became more diverse with the intervention, indicating improved access to CMM pharmacists. Cultivating relationships among patients with greater social disadvantage and cardiovascular disease and CMM pharmacists may improve health outcomes and connect patients to essential resources, thus potentially improving long-term cardiovascular outcomes.
Rapid Online Data Collection and Reporting to Local Health Departments during the Pandemic: The COVID-19 Outbreak Public Evaluation (COPE) Initiative SARS-CoV-2 Case Surveys
Authors: Booker Lauren A. , Czeisler Mark É. , Lane Rashon I. , Orellana Robert C. , Lundeen Kristen , Macomber Kathryn , Collins Jim , Varma Prerna , Rajaratnam Shantha M.W. , Howard Mark E. , Czeisler Charles A. , Weaver Matthew D.
Published: July 2024

Objectives:

To develop and implement a pilot online data collection tool to help local health departments with their COVID-19 pandemic response efforts and inform health department actions.

Design:

The COVID-19 Outbreak Public Evaluation (COPE) was an online survey and was distributed by participating sites to individuals who recently tested positive for SARS-CoV-2. Surveys recorded participant demographics and assessed recent infection risk behaviors (eg, mask use, air travel), vaccination status, sleep and exercise habits, social behaviors and beliefs, and physical and mental health.

Setting:

Seven health departments participated in the initiative, which took place during May 1 to September 30, 2022. Identical items were administered to demographically representative samples of adults nationally in the United States within a similar timeframe.

Participants:

A total of 38 555 participants completed surveys. Responses from participants with recent SARS-CoV-2 infections were compared with respondents from the national surveys who did not have evidence or awareness of prior SARS-CoV-2 infections.

Main outcome measure:

To implement of a process that allows health departments to receive data from local cases and compare this information to national controls during the COVID-19 pandemic.

Results:

Fifty-four biweekly reports were provided to public health departments between May and September 2022. Information and comparisons within the reports were updated in response to evolving public health priorities for the pandemic response. The initiative helped to guide public health response efforts during the COVID-19 pandemic. Moreover, the receptiveness by local health departments and participants provides evidence to support this data collection and reporting model as a component of the public health response to future emergencies.

Conclusion:

This project demonstrates the feasibility of a centralized, rapid, and adaptive data collection system for local health departments and provides evidence to advocate for data collection methods to help guide local health departments to respond in a timely and effective manner to future public health emergencies.
Repeated Exposure to COVID-19 Misinformation: A Longitudinal Analysis of Prevalence and Predictors in a Community Sample
Authors: Weng Olivia , Johnson Kimberly J. , Kreuter Matthew W.
Published: July 2024

Belief in health misinformation can affect individual health decisions and actions. Repeated exposure to the same misinformation strengthens its impact, yet little is known about how commonly repeated exposure occurs. To estimate the prevalence, we tracked exposure to 5 inaccurate COVID-19 claims every week for up to 23 consecutive weeks in a racially diverse panel of adults (n = 213). Repeated exposure was common: across the 5 claims, 10%-43% of respondents reported hearing the misinformation in ≥ 3 different weeks. Frontline workers were more likely than other community members to experience repeated exposure, with adjusted incidence rate ratios (IRRs) ranging from 1.8 to 4.9 across the 4 items. Repeated exposure was most common among older adults. Adjusted IRR for those ages ≥ 50 versus 18-29 years ranged from 1.8 to 2.5 per misinformation claim. Public health planning efforts to counter health misinformation should anticipate multiple exposures to the same false claim, especially in certain subgroups.
T3N0 Rectal Cancer
Authors: Chalmers Zachary R. , Roberts Hannah J. , Wo Jennifer Y.
Published: July 2024

The optimal management of T3N0 rectal cancer is an area of active debate that has withstood multiple decades of research. In this comprehensive review, we delve into the many nuances that come with treating T3N0 rectal cancer, particularly examining the role and evolution of radiation therapy. We review both the historical paradigms and latest advances in treatment and highlight the significance of precise preoperative staging. As the field continues to evolve, this review highlights a shift toward more tailored treatments, considering both patient goals and the desire for optimal oncologic outcomes. In the current era, clinical decision-making for T3N0 rectal cancer requires a patient-centric approach that balances effective therapy while minimizing undue side effects.
Nonoperative Management for Rectal Cancer
Authors: Pollom Erqi L. , Sheth Vipul R. , Dawes Aaron J. , Holden Thomas
Published: July 2024

The treatment paradigm for rectal cancer has been shifting toward de-escalated approaches to preserve patient quality of life. Historically, the standard treatment in the United States for locally advanced rectal cancer has standardly comprised preoperative chemoradiotherapy coupled with total mesorectal excision. Recent data challenge this “one-size-fits-all” strategy, supporting the possibility of omitting surgery for certain patients who achieve a clinical complete response to neoadjuvant therapy. Consequently, patients and their physicians must navigate diverse neoadjuvant options, often in the context of pursuing organ preservation. Total neoadjuvant therapy, involving the administration of all chemotherapy and radiation before total mesorectal excision, is associated with the highest rates of clinical complete response. However, questions persist regarding the optimal sequencing of radiation and chemotherapy and the choice between short-course and long-course radiation. Additionally, meticulous response assessment and surveillance are critical for selecting patients for nonoperative management without compromising the excellent cure rates associated with trimodality therapy. As nonoperative management becomes increasingly recognized as a standard-of-care treatment option for patients with rectal cancer, ongoing research in patient selection and monitoring as well as patient-reported outcomes is critical to guide personalized rectal cancer management within a patient-centered framework.
Treatment of Locally Recurrent Rectal Cancer
Authors: Regan Samuel N. , Hendren Samantha , Krauss John C. , Crysler Oxana V. , Cuneo Kyle C.
Published: July 2024

Up to 10% of patients with locally advanced rectal cancer will experience locoregional recurrence. In the setting of prior surgery and often radiation and chemotherapy, these represent uniquely challenging cases. When feasible, surgical resection offers the best chance for oncologic control yet risks significant morbidity. Studies have consistently indicated that a negative surgical resection margin is the strongest predictor of oncologic outcomes. Chemoradiation is often recommended to increase the chance of an R0 resection, and in cases of close/positive margins, intraoperative radiation/brachytherapy can be utilized. In patients who are not surgical candidates, radiation can provide symptomatic relief. Ongoing phase III trials are aiming to address questions regarding the role of reirradiation and induction multiagent chemotherapy regimens in this population.
Point/Counterpoint #1
Authors: Kumar Abhishek , Palta Manisha , Jia Jingquan
Published: July 2024

For decades, the standard neoadjuvant therapy regimen for locally advanced rectal cancer consisted of chemoradiation, surgical resection, and consideration of adjuvant systemic therapy. Additional data have emerged suggesting neoadjuvant systemic therapy as a reasonable alternative to chemoradiation in selected patients. In addition, a total neoadjuvant therapy approach integrating both chemotherapy and chemoradiation results in superior cancer outcomes and the potential for consideration of nonoperative management in patients with a clinical complete response. Despite a multitude of therapeutic pathways for the management of rectal cancer, what is clear, however, is the importance of a multidisciplinary approach with shared patient and provider decision-making.
The Use of Frailty Scores for Screening the Surgical Risk Benefits
Authors: Ballacchino Madison M. , McQuestion Chloe C. , Giuca Matthew S. , Dosluoglu Hasan H. , Nader Nader D.
Published: July 2024

Objective:

Our study aims to examine the role of multi-disciplinary surgical pause committees (MDSPC) in perioperative planning to reduce adverse postoperative events and mortality rates.

Summary Background Data:

Frail patients could benefit from preoperative MDSPCs when utilizing risk-benefit ratios for the proposed surgical plan. We examined whether MDSPCs improved clinical outcomes by developing individualized care plans and stratifying patients based on their level of frailty and ability to overcome external stressors.

Methods:

We retrospectively collected patient information after MDSPC evaluation, at our medical center for 12 years since 2011. Patient’s frailty risk assessment index (RAI) scores were calculated, and survival status was updated. MDSPCs plans were put into the following categories: proceed with the planned surgery (G1), proceed after medical optimization (G2), reduce invasiveness of surgery or anesthesia plan (G3), or adopt a non-surgical approach (G4). Chi-square and independent t-tests were used for categorical and numerical data, respectively. Survival analysis for 30-day (primary endpoint), one-year, and overall mortality rates used Kaplan-Meier. The alpha was set at 0.05.

Results:

Clinical information was accessed from 12 women and 382 men. The average age was 71±11 years. 87.3% of planned surgical operations were stratified as ASA class III and IV. RAI scores were 36.4±9.6 (G1), similar to 37.4±10.8 (G2) but lower than 41.4±9.3 (G3) and 44.2±9.7 (G4) (P<0.001). Average survival duration was 35 months (G1), 35 months (G2), both significantly longer than 20 months (G3) and 18 months (G4) (P<0.001).

Conclusion:

Medical optimization improved overall survival and reduced death within 30 days and one year to be comparable to G1. Additionally, reducing the surgical invasiveness only improved survival advantage for six months, after which it was comparable to those in G4 with the worst outcome. RAI scoring is an excellent tool to predict the outcome of surgery, and it was used successfully in critically ill patients.
Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito
Anopheles gambiae
Authors: Ito Ryo , Kamiya Masaki , Takayama Koichi , Mori Sumito , Matsumoto Rei , Takebayashi Mayuka , Ojima Hisanori , Fujimura Shota , Yamamoto Haruki , Ohno Masayuki , Ihara Makoto , Okajima Toshihide , Yamashita Atsuko , Colman Fraser , Lycett Gareth J. , Sattelle David B. , Matsuda Kazuhiko
Published: July 2024

With the spread of resistance to long-established insecticides targeting
Anopheles
malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13
Anopheles gambiae
nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Ag
α
1, Ag
α
2, Ag
α
3, Ag
α
8 and Ag
β
1 subunits in
Xenopus laevis
oocytes, the
Drosophila melanogaster
orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Ag
α
2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Ag
α
3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Ag
α
1/Ag
α
2/Ag
α
8/Ag
β
1 nAChR, their hydrophobicity and their rate of knockdown of adult female
An. gambiae
, providing new insights into neonicotinoid features important for malaria vector control.
A novel FAM83G variant from palmoplantar keratoderma patient disrupts WNT signalling via loss of FAM83G-CK1α interaction
Authors: Glennie Lorraine , Solà Marta Codina , Xunclà Mar , Español Gloria Aparicio , Garcia-Arumí Elena , Tizzano Eduardo Fidel , Wood Nicola T. , Macartney Thomas J. , Lasa-Aranzasti Amaia , Sapkota Gopal P.
Published: July 2024

Palmoplantar keratoderma (PPK) is a multi-faceted skin disorder characterized by the thickening of the epidermis and abrasions on the palms and soles of the feet. Among the genetic causes, biallelic pathogenic variants in the
FAM83G
gene have been associated with PPK in dogs and humans. Here, a novel homozygous variant (c.794G>C, p.Arg265Pro) in the
FAM83G
gene, identified by whole exome sequencing in a 60-year-old female patient with PPK, is reported. The patient exhibited alterations in the skin of both hands and feet, dystrophic nails, thin, curly and sparse hair, long upper eyelid eyelashes, and poor dental enamel. FAM83G activates WNT signalling through association with ser/thr protein kinase CK1α. When expressed in FAM83G
−/−
DLD1 colorectal cancer cells, the FAM83G
R265P
variant displayed poor stability, a loss of interaction with CK1α and attenuated WNT signalling response. These defects persisted in skin fibroblast cells derived from the patient. Our findings imply that the loss of FAM83G-CK1α interaction and subsequent attenuation of WNT signalling underlie the pathogenesis of PPK caused by the FAM83G
R265P
variant.
Developing phytocompound-based new drugs against multi-drug-resistant
Staphylococcus aureus
Authors: Shuvo Md. Nazmussakib , Halder Sajal Kumar , Alam Nuhu , Himel Mahbubul Kabir , Shil Aparna
Published: July 2024

Staphylococcus aureus
, a prevalent component of the human microbiota, is associated with skin infections to life-threatening diseases, presenting challenges in treatment options and necessitating the development of effective treatments. This study integrated computational and
in vitro
approaches to identify promising phytocompounds with therapeutic potential. Staphopain B emerged as a target protein for its role in immune evasion, exhibiting stability during molecular dynamic simulation (MDS) with a root mean square deviation value of 2.376 Å. Screening 115 phytocompounds with antibacterial properties from the PubChem database identified 12 with drug-like properties, nine of which showed superior binding affinity to Staphopain B compared to a commercial antibiotic, doxycycline (−7.8 kcal mol
−1
). Notably, epoxyazadiradione and nimbolide displayed higher estimated free energy of binding scores (−7.91 and −7.93 kcal mol
−1
, respectively), indicating strong protein–ligand interactions. The root mean square fluctuation values for epoxyazadiradione and nimbolide were 1.097 and 1.034 Å, respectively, which was confirmed through MDS. Crude ethanolic extracts (100% and 70%) of neem (
Azadirachta indica
) leaves demonstrated narrow inhibition against the bacteria in comparison to doxycycline in the disc-diffusion assay. This study underscores the potential of phytocompounds as therapeutic agents against
S. aureus
; however, further
in vitro
experiments and testing of the phytocompounds
in vivo
are required.
Subjective evidence evaluation survey for many-analysts studies
Authors: Sarafoglou Alexandra , Hoogeveen Suzanne , van den Bergh Don , Aczel Balazs , Albers Casper J. , Althoff Tim , Botvinik-Nezer Rotem , Busch Niko A. , Cataldo Andrea M. , Devezer Berna , van Dongen Noah N. N. , Dreber Anna , Fried Eiko I. , Hoekstra Rink , Hoffman Sabine , Holzmeister Felix , Huber Jürgen , Huntington-Klein Nick , Ioannidis John , Johannesson Magnus , Kirchler Michael , Loken Eric , Mangin Jan-Francois , Matzke Dora , Menkveld Albert J. , Nilsonne Gustav , van Ravenzwaaij Don , Schweinsberg Martin , Schulz-Kuempel Hannah , Shanks David R. , Simons Daniel J. , Spellman Barbara A. , Stoevenbelt Andrea H. , Szaszi Barnabas , Trübutschek Darinka , Tuerlinckx Francis , Uhlmann Eric L. , Vanpaemel Wolf , Wicherts Jelte , Wagenmakers Eric-Jan
Published: July 2024

Many-analysts studies explore how well an empirical claim withstands plausible alternative analyses of the same dataset by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g. effect size) provided by each analysis team. Although informative about the range of plausible effects in a dataset, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item subjective evidence evaluation survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous many-analysts study.
Multi-proxy bioarchaeological analysis of skeletal remains shows genetic discontinuity in a Medieval Sicilian community
Authors: Monnereau Aurore , Ughi Alice , Orecchioni Paola , Hagan Richard , Talbot Helen M. , Nikita Efthymia , Hamilton Derek , Le Roux Petrus , Molinari Alessandra , Carver Martin , Craig Oliver E. , Speller Camilla F. , Alexander Michelle M. , Wales Nathan
Published: July 2024

The medieval period in Sicily was turbulent, involving successive regime changes, from Byzantine (Greek Christian), Aghlabid (Sunni Muslim), Fatimid (Shīʿa Muslim), to Normans and Swabians (Latin Christian). To shed new light on the local implications of regime changes, we conducted a multidisciplinary analysis of 27 individuals buried in adjacent Muslim and Christian cemeteries at the site of Segesta, western Sicily. By combining radiocarbon dating, genome-wide sequencing, stable and radiogenic isotopic data, and archaeological records, we uncover genetic differences between the two communities but find evidence of continuity in other aspects of life. Historical and archaeological evidence shows a Muslim community was present by the 12th century during Norman governance, with the Christian settlement appearing in the 13th century under Swabian governance. A Bayesian analysis of radiocarbon dates from the burials finds the abandonment of the Muslim cemetery likely occurred after the establishment of the Christian cemetery, indicating that individuals of both faiths were present in the area in the first half of the 13th century. The biomolecular results suggest the Christians remained genetically distinct from the Muslim community at Segesta while following a substantially similar diet. This study demonstrates that medieval regime changes had major impacts beyond the political core, leading to demographic changes while economic systems persisted and new social relationships emerged.
Sexual selection may support phenotypic plasticity in male coloration of an African cichlid fish
Authors: Dijkstra Peter D. , Funnell Tyler R. , Fialkowski Robert J. , Piefke Taylor J. , Border Shana E. , Aufdemberge Phil M. , Hartman Hailey A.
Published: July 2024

The expression of sexually selected traits, such as ornaments or body coloration, is often influenced by environmental conditions. While such phenotypic plasticity is often thought to precede evolutionary change, plasticity itself can also be a target of selection. However, the selective forces supporting the evolution and persistence of plasticity in sexual traits are often unclear. Using the cichlid fish
Astatotilapia burtoni
, we show that variation in the level of mate competition may promote plasticity in body coloration. In this species, males can change between yellow and blue colour. We found that experimentally increased competition over mating territories led to a higher proportion of males expressing the yellow phenotype. The expression of yellow coloration was found to be beneficial because yellow males won more staged dyadic contests and exhibited a lower level of oxidative stress than blue males. However, females were more likely to spawn with blue males in mate choice experiments, suggesting that expression of blue coloration is sexually more attractive. The ability to adjust colour phenotype according to the local competitive environment could therefore promote the persistence of plasticity in coloration.
MICROBIAL FLORA OF THE RESPIRATORY TRACT AND SKIN OF ARTISANAL MUNICIPAL SOLID WASTE HANDLERS IN ABA, ABIA STATE, NIGERIA.
Authors: Nwankwo Ifeanyichukwu Wilson , Nwachukwu Nkechi C , Onwuchekwa Elendu C , Okamgba Okezie Caleb , Ugbogu Ositadinma Chinyere
Published: July 2024

Municipal solid waste handling carries occupational risk for waste handlers due to exposure to diverse microorganisms and hazardous substances which cause respiratory and skin infections. This study assessed the sociodemographic characteristics, health-related complaints, health-seeking behaviour and the bacterial and fungal microflora of the respiratory tract and skin of artisanal municipal solid waste handlers and some controls in Aba, Nigeria. This cross-sectional study recruited 150 respondents using simple random sampling technique. Ethical clearance and informed consent of participants were obtained. An interviewer administered structured questionnaire was used to obtain relevant information and data were statistically analyzed using IBM SPSS version 25. Nasal and skin swabs were collected for culture and isolation of bacteria and fungi colonizing the respiratory tract and skin of the study subjects using bacteria and fungi culture media. Findings show that Municipal solid waste handling in Aba is mostly carried out by males (95%). The mean age of the waste handlers is 30 years, with the age group of 21-40 years constituting the highest proportion (65%) of the workforce. Health-related complaints were higher (95%) amongst the waste handlers compared to the control subjects (4%). Findings show high prevalence of respiratory (57%), eye (34%) and skin (87%) complaints among the waste workers compared to 6%, 0%, and 2% respectively among the control subjects. Majority (78%) of the waste workers indulge in self-medication via over the counter (OTC) drugs, 17% access diagnostic laboratories and only 4% visit hospitals for treatment as against the control subjects that recorded 2% for OTC drugs, 92% (Laboratories) and 4% (hospitals). Acquisition (15%) and use (3%) of personal protective equipment (PPE) were very low amongst the waste handlers. 704 bacterial isolates and 191 fungal organisms were obtained from the study subjects. S. epidermidis (24%), B. cereus (13%) and S.aureus (29%), S. epidermidis (19%) predominated in the respiratory tract and skin respectively, of the waste handlers. Similarly, S. aureus (34.3%), B. cereus (20.9%) and B. cereus (37.9%), S. epidermidis (18.1%) predominated the respiratory tract and skin respectively among the control subjects. Candida spp was most predominant fungi in the respiratory tract (81.4%) and skin (42.9%) of the waste handlers as well as in the respiratory tract (85%) and skin (78%) of the controls. Colonization by bacteria and fungi following occupational exposure to waste results in high prevalence of health complaints among the waster handlers and this may be connected to the low use of PPE and poor health seeking behaviour. Health education, sensitization and improvement in working conditions are necessary to mitigate the occupational challenges of the waste handlers.
Ex vivo model of breast cancer cell invasion in live lymph node tissue
Authors: Morgaenko Katerina , Arneja Abhinav , Ball Alexander G. , Putelo Audrey M. , Munson Jennifer M. , Rutkowski Melanie R. , Pompano Rebecca R.
Published: July 2024

Lymph nodes (LNs) are common sites of metastatic invasion in breast cancer, often preceding spread to distant organs and serving as key indicators of clinical disease progression. However, the mechanisms of cancer cell invasion into LNs are not well understood. Existing in vivo models struggle to isolate the specific impacts of the tumor-draining lymph node (TDLN) milieu on cancer cell invasion due to the co-evolving relationship between TDLNs and the upstream tumor. To address these limitations, we used live ex vivo LN tissue slices with intact chemotactic function to model cancer cell spread within a spatially organized microenvironment. After showing that BRPKp110 breast cancer cells were chemoattracted to factors secreted by naïve LN tissue in a 3D migration assay, we demonstrated that ex vivo LN slices could support cancer cell seeding, invasion, and spread. This novel approach revealed dynamic, preferential cancer cell invasion within specific anatomical regions of LNs, particularly the subcapsular sinus (SCS) and cortex, as well as chemokine-rich domains of immobilized CXCL13 and CCL1. While CXCR5 was necessary for a portion of BRPKp110 invasion into naïve LNs, disruption of CXCR5/CXCL13 signaling alone was insufficient to prevent invasion towards CXCL13-rich domains. Finally, we extended this system to pre-metastatic TDLNs, where the ex vivo model predicted a lower invasion of cancer cells. The reduced invasion was not due to diminished chemokine secretion, but it correlated with elevated intranodal IL-21. In summary, this innovative ex vivo model of cancer cell spread in live LN slices provides a platform to investigate cancer invasion within the intricate tissue microenvironment, supporting time-course analysis and parallel read-outs. We anticipate that this system will enable further research into cancer-immune interactions and allow isolation of specific factors that make TDLNs resistant to cancer cell invasion, which are challenging to dissect in vivo.
Graphene-based micro-electrodes with reinforced interfaces and tunable porous structures for improved neural recordings
Authors: Dong Miheng , Yang Junjun , Zhen Fangzheng , Du Yu , Ding Siyuan , Yu Aibing , Zou Ruiping , Qiu Ling , Guo Zhijun , Coleman Harold A. , Parkington Helena C. , Fallon James B. , Forsythe John S. , Liu Minsu
Published: July 2024

Invasive neural electrodes prepared from materials with miniaturized geometrical size could improve the longevity of implants by reducing the chronic inflammatory response. Graphene-based microfibers with tunable porous structures have a large electrochemical surface area (ESA)/geometrical surface area (GSA) ratio that has been reported to possess low impedance and high charge injection capacity (CIC), yet the control of the porous structure remains to be fully investigated. In this study, we introduce wet-spun graphene-based electrodes with pores tuned by sucrose concentrations in the coagulation bath. The electrochemical properties of thermally reduced rGO were optimized by adjusting the ratio of rGO to sucrose, resulting in significantly lower impedance, higher CIC, and higher charge storage capacity (CSC) than platinum microwires. Tensile and insertion tests confirmed that optimized electrodes had sufficient strength to ensure a 100% insertion success rate with low angle shift, thus allowing precise implantation without the need for additional mechanical enhancement. Acutein-vivorecordings from the auditory cortex found low impedance benefits from the recorded amplitude of spikes, leading to an increase in the signal-to-noise ratio (SNR).Ex-vivorecordings from hippocampal brain slices demonstrate that it is possible to record and/or stimulate with graphene-based electrodes with good fidelity compared with conventional electrodes.
Multiple Independent Genetic Code Reassignments of the UAG Stop Codon in Phyllopharyngean Ciliates
Authors: McGowan Jamie , Richards Thomas A. , Hall Neil , Swarbreck David
Published: July 2024

The translation of nucleotide sequences into amino acid sequences, governed by the genetic code, is one of the most conserved features of molecular biology. The standard genetic code, which uses 61 sense codons to encode one of the 20 standard amino acids and 3 stop codons (UAA, UAG, and UGA) to terminate translation, is used by most extant organisms. The protistan phyla Ciliophora (the ‘ciliates’) are an unusual exception to this norm, exhibiting the greatest diversity of non-canonical nuclear genetic code variants and evidence of repeated changes in code. In this study, we report the discovery of multiple independent genetic code changes within the Phyllopharyngea class of ciliates. By mining publicly available ciliate genome datasets, we discovered that three ciliate species from the TARA Oceans eukaryotic metagenome dataset use the UAG codon to putatively encode leucine. We identified novel suppressor tRNA genes in two of these genomes. Phylogenomics analysis revealed that these three uncultivated taxa form a monophyletic lineage within the Phyllopharyngea class. Expanding our analysis by reassembling published phyllopharyngean genome datasets led to the discovery that the UAG codon had also been reassigned to putatively code for glutamine inHartmannula sinicaandTrochilia petrani. Phylogenomics analysis suggests that this occurred via two independent genetic code change events. These data demonstrate that the reassigned UAG codons have widespread usage as sense codons within the phyllopharyngean ciliates. Furthermore, we show that the function of UAA is firmly fixed as the preferred stop codon. These findings shed light on the evolvability of the genetic code in understudied microbial eukaryotes.
Waves of Colonization and Gene Flow in a Great Speciator
Authors: Gyllenhaal Ethan F. , Brady Serina S. , DeCicco Lucas H. , Naikatini Alivereti , Hime Paul M. , Manthey Joseph D. , Kelly John , Moyle Robert G. , Andersen Michael J.
Published: July 2024

Secondary contact between previously allopatric lineages offers a test of reproductive isolating mechanisms that may have accrued in isolation. Such instances of contact can produce stable hybrid zones—where reproductive isolation can further develop via reinforcement or phenotypic displacement—or result in the lineages merging. Ongoing secondary contact is most visible in continental systems, where steady input from parental taxa can occur readily. In oceanic island systems, however, secondary contact between closely related species of birds is relatively rare. When observed on sufficiently small islands, relative to population size, secondary contact likely represents a recent phenomenon. Here, we examine the dynamics of a group of birds whose apparent widespread hybridization influenced Ernst Mayr’s foundational work on allopatric speciation: the whistlers of Fiji (Aves:Pachycephala). We demonstrate two clear instances of secondary contact within the Fijian archipelago, one resulting in a hybrid zone on a larger island, and the other resulting in a wholly admixed population on a smaller, adjacent island. We leveraged low genome-wide divergence in the hybrid zone to pinpoint a single genomic region associated with observed phenotypic differences. We use genomic data to present a new hypothesis that emphasizes rapid plumage evolution and post-divergence gene flow.
Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality
Authors: Cunningham Chelsea E. , Vizeacoumar Frederick S. , Zhang Yue , Kyrylenko Liliia , Gao Peng , Maranda Vincent , Dong He , Price Jared DW , Ganapathysamy Ashtalakshmi , Hari Rithik , Denomy Connor , Both Simon , Wagner Konrad , Wu Yingwen , Khan Faizaan , Mosley Shayla , Chen Angie , Katrii Tetiana , Zoller Ben G. E. , Rajamanickam Karthic , Walke Prachi , Gong Lihui , Patel Hardikkumar , Lazell-Wright Mary , Morales Alain Morejon , Bhanumathy Kalpana K. , Elhasasna Hussain , Dahiya Renuka , Abuhussein Omar , Dmitriev Anton , Freywald Tanya , Munhoz Erika Prando , Krishnan Anand , Ruppin Eytan , Lee Joo Sang , Rox Katharina , Toosi Behzad , Koebel Martin , Kinloch Mary , Hopkins Laura , Lee Cheng Han , Datla Raju , Yadav Sunil , Wu Yuliang , Baker Kristi , Empting Martin , Kiemer Alexandra K. , Freywald Andrew , Vizeacoumar Franco J.
Published: July 2024

Tumor heterogeneity poses a significant challenge in combating treatment resistance. Despite Polo-like kinase 1 (PLK1) being universally overexpressed in cancers and contributing to chromosomal instability (CIN), direct PLK1 inhibition hasn’t yielded clinical progress. To address this, we utilized the synthetic dosage lethality (SDL) approach, targeting PLK1’s genetic interactions for selective killing of overexpressed tumor cells while mitigating heterogeneity-associated challenges. Employing computational methods, we conducted a genome-wide shRNA screen, identifying 105 SDL candidates. Further in vivo CRISPR screening in a breast cancer xenograft model and in vitro CRISPR analysis validated these candidates. Employing Perturb-seq revealed IGF2BP2/IMP2 as a key SDL hit eliminating PLK1-overexpressing cells. Suppression of IGF2BP2, genetically or pharmacologically, downregulated PLK1 and limited tumor growth. Our findings strongly propose targeting PLK1’s genetic interactions as a promising therapeutic approach, holding broad implications across multiple cancers where PLK1 is overexpressed.
How do we imagine a speech? A triple network model for situationally simulated inner speech
Authors: Gao Xiaowei , Yang Junjie , Li Chaoqun , Guo Xiaolin , Wang Yaling , Qu Zhiheng , Li Wanchun , Liu Jiaxuan , Li Zhongqi , Li Wanjing , Hu Zhe , Li Junjing , Huang Yien , Chen Jiali , Wen Hao , Zhao Zehao , Kaiser Daniel , Wei Tao , Yuan Binke
Published: July 2024

Inner speech is a silent verbal experience and plays central roles in human consciousness and cognition. Despite impressive studies over the past decades, the neural mechanisms of inner speech remain largely unknown. In this study, we adopted an ecological paradigm called situationally simulated inner speech. Unlike mere imaging speech of words, situationally simulated inner speech involves the dynamic integration of contextual background, episodic and semantic memories, and external events into a coherent structure. We conducted dynamic activation and network analyses on fMRI data, where participants were instructed to engage in inner speech prompted by cue words across 10 different contextual backgrounds. Our seed-based co-activation pattern analyses revealed dynamic involvement of the language network, sensorimotor network, and default mode network in situationally simulated inner speech. Additionally, frame-wise dynamic conditional correlation analysis uncovered four temporal-reoccurring states with distinct functional connectivity patterns among these networks. We proposed a triple network model for deliberate inner speech, including language network for a truncated form of overt speech, sensorimotor network for perceptual simulation and monitoring, and default model network for integration and ‘sense-making’ processing.

Highlights

In ten contextual backgrounds, subjects were instructed to perform situationally simulated inner speech based on cue words.

The ventral parts of the bilateral somatosensory areas and middle superior temporal gyrus were as centers for seed-based co-activation pattern analyses.

A triple network model of language network, sensorimotor network, and default mode network was proposed for deliberate inner speech.
Initial TCR Signal Strength Imprints GATA3 and Tbet Expression Driving T-helper Cell Fate Decisions
Authors: Al-Aghbar Mohammad Ameen , Khan Taushif , Guarch Meritxell Espino , Palmer Douglas C , van Panhuys Nicholas
Published: July 2024

With the exception of the T-helper 2 (Th2) subset, cytokine driven pathways provide a robust mechanistic explanation for the observed outcomes of CD4+ T-cell differentiation. Using a quantitative model of activation, we studied the integration of TCR-signal-strength with cytokine signalling during Th2 differentiation. Upon the initial activation of Th-naïve cells, TCR signalling was found to set early expression levels for the master regulators of differentiation Tbet and GATA3, independent of the presence of polarizing cytokines.

Subsequently cytokine stimuli modulated transcription factor (TF) expression levels to tune the outcome of differentiation. Here, weak TCR signalling was sufficient to drive the early upregulation of GATA3 and induce Th2 differentiation, in an IL-4 independent manner. Th1 differentiation was however shown to require additional cytokine signalling input, either in the form of autocrine IFNγ or exogenous IL-12. Using mathematical modelling we demonstrate that T-helper differentiation occurs along a continuum of states. Set by the relative co-expression of regulatory TFs, where effector cytokine production is controlled in a probabilistic manner determined by the relative levels GATA3 and Tbet expressed.

Together, our data indicate TCR signalling inputs drive an early bifurcation in the T-helper differentiation pathway. Together, the integration of TCR signal strength with cytokine inputs act as a mechanism for the detection of immuno-evasive parasitic infections, whilst providing an additional checkpoint to prevent aberrant Th1 associated immunopathology.