bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into ischemia-reperfusion injury signaling pathways in organ transplantation
Authors: Dery Kenneth J. , Kupiec-Weglinski Jerzy W.
Published: July 2022

Purpose of review

Ischemia-reperfusion injury (IRI) leading to allograft rejection in solid organ transplant recipients is a devastating event that compromises graft and patient survival. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers translating to important therapeutic intervention remains a challenge. This review will summarize recent findings in this area.

Recent findings

In the past 18 months, our understanding of organ transplantation IRI has improved. IRI involves a positive amplification feedback loop encompassing damaged cells at the graft site, the activity of redox-sensitive damage-associated molecular patterns, and local sequestration of recipient-derived monocytes, lymphocytes and polymorphonuclear leukocytes, like neutrophils, to sustain the immunological cascade and to enhance the destruction of the foreign tissue. Recent studies have identified critical components leading to IRI, including the oxidation state of high mobility group box 1, a classic danger signal, its role in the Toll-like receptor 4–interleukin (IL)-23–IL-17A signaling axis, and the role of neutrophils and CD321, a marker for transmigration of circulating leukocytes into the inflamed tissue. In addition, recent findings imply that the protective functions mediated by autophagy activation counterbalance the detrimental nucleotide-binding domain-like receptor family, pyrin domain containing 3 inflammasome pathway. Finally, clinical studies reveal the posttransplant variables associated with early allograft dysfunction and IRI.

The future challenge will be understanding how crosstalk at the molecular and cellular levels integrate prospectively to predict which peri-transplant signals are essential for long-term clinical outcomes.
Genetics of testicular cancer: a review
Authors: Martin Felicity C. , Conduit Ciara , Loveland Kate L. , Thomas Benjamin , Lewin Jeremy , Tran Ben
Published: July 2022

Purpose of review

Testicular germ cell tumours (TGCTs) are the most common solid malignant cancer diagnosed in young males and the incidence is increasing. Understanding the genetic basis of this disease will help us to navigate the challenges of early detection, diagnosis, treatment, surveillance, and long-term outcomes for patients.

Recent findings

TGCTs are highly heritable. Current understanding of germline risk includes the identification of one moderate-penetrance predisposition gene, checkpoint kinase 2 (CHEK2), and 78 low-to-moderate-risk single nucleotide polymorphisms identified in genome-wide-associated studies, which account for 44% of familial risk. Biomarker research in TGCTs has been challenging for multiple reasons: oncogenesis is complex, actionable mutations are uncommon, clonal evolution unpredictable and tumours can be histologically and molecularly heterogeneous. Three somatic mutations have thus far been identified by DNA exome sequencing, exclusively in seminomas: KIT, KRAS and NRAS. Several genetic markers appear to be associated with risk of TGCT and treatment resistance. TP53 mutations appear to be associated with platinum resistance. MicroRNA expression may be a useful biomarker of residual disease and relapse in future.

The biology of testicular germ cells tumours is complex, and further research is needed to fully explain the high heritability of these cancers, as well as the molecular signatures which may drive their biological behaviour.
Micropapillary bladder cancer: an evolving biology
Authors: Lonati Chiara , Simeone Claudio , Suardi Nazareno , Briganti Alberto , Montorsi Francesco , Moschini Marco
Published: July 2022

Purpose of review

To summarize a comprehensive overview of more recent evidence on micropapillary bladder cancer (MPBC), focusing on actual incidence, clinical features, therapeutic strategies, and prognosis.

Recent findings

MPBC generally exhibits an aggressive behaviour compared with pure urothelial carcinoma (pUC) with advances in tumour stage and nodal and distant spread at diagnosis. Due to its rarity and presence of only small sample size and retrospective studies, no consensus currently exists regarding the most effective therapeutic strategy to be performed among nonmuscle-invasive (conservative treatment versus immediate radical cystectomy) and muscle-invasive MPBC (neoadjuvant therapy versus upfront radical cystectomy versus adjuvant chemotherapy).

The incidence of MPBC is recently increased according to latter literature, ranging from 2.9 to 7.6% of all bladder cancer. Despite its aggressive behaviour at time of presentation, more recent evidence fails to demonstrate a significant association between MPBC and worse outcomes compared with pUC when adjusted for clinical and pathological features. According to latter evidence, MPBC pathological response to NAC appears to be unsatisfactory compared with pUC patients while neoadjuvant immunotherapy with Pembrolizumab may represent an effective treatment among MPBC patients, based on PD-L1 and TMB expression.
Novel germline mutations for active surveillance and imaging strategies in prostate cancer
Authors: Mondschein Romy , Taylor Renea , Thorne Heather , Bolton Damien
Published: July 2022

Purpose of review

This review highlights the emerging role of genetics-lead medicine (GLM) in prostate cancer. We describe the benefits of GLM integration into prostate cancer screening, diagnosis and management. Imaging techniques enhancing prostate cancer detection are advancing concurrently, facilitating strategic active surveillance protocols for appropriately selected patients. We aim to improve clinician awareness of the role of GLM in current and future practice.

Recent findings

We explore recent literature advancing the role of GLM in prostate cancer detection and management, particularly as this coexists with the development of imaging technology. Our current understanding of germline mutations implicated in familial prostate cancer development is summarized. We describe how these developments are being utilized to inform screening, surveillance and the development of novel therapies. We summarize current guidelines and explore factors inhibiting optimal implementation of recommendations in clinical practice.

Integration and further development of genetics-lead medicine in the detection, surveillance and management of prostate cancer will improve clinical outcomes for men at risk of aggressive disease as a result of familial predispositions to prostate cancer. This review summarizes the pertinent developments in the field including improving clinician awareness to facilitate implantation of these strategies into current clinical practice.
Incidence and Risk Factors for New-Onset Diabetes Mellitus After Surgical Resection of Pancreatic Cystic Lesions
Authors: Firkins Stephen A. , Hart Phil A. , Porter Kyle , Chiang ChienWei , Cloyd Jordan M. , Dillhoff Mary , Lara Luis F. , Manilchuk Andrei , Papachristou Georgios I. , Pawlik Timothy M. , Tsung Allan , Conwell Darwin L. , Krishna Somashekar G.
Published: July 2022

Objectives

There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs.

Methods

We utilized the IBM MarketScan Database (2012–2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs. Patients with any other pancreatic disease were excluded. We performed Kaplan-Meier analysis and multivariable Cox proportional hazards regression to define the incidence and risk factors of postoperative NODM.

Results

Among 311 patients, the overall risk (95% confidence interval) of NODM was 9.1% (6.3–12.9%), 15.1% (11.3–20.2%), and 20.2% (15.3–26.4%) at 6, 12 and 24 months, respectively. Multivariable analysis (adjusted hazard ratio; 95% confidence interval) revealed that older age (1.97; 1.04–3.72; 55–64 vs 18–54 years), obesity (2.63; 1.35–5.12), hypertension (1.79; 1.01–3.17), and cardiovascular disease (2.54; 1.02–6.28) were independent predictors of NODM. Rates of NODM were similar after distal pancreatectomy versus pancreaticoduodenectomy.

Conclusions

Within 2 years, 1 in 5 patients without any other pancreatic disease will develop NODM after partial pancreatectomy for PCLs. Those with advanced age, metabolic syndrome features, and/or cardiovascular disease may benefit from preoperative counseling and intensive postoperative monitoring, education, and treatment for diabetes mellitus.
Subject Matter Expert Nurses in Safe Sleep Program Implementation
Authors: Stringer Marilyn , Ohnishi Bonnie Renner , Ferrarello Deborah , Lazzeri Jessica , Giordano Nicholas A. , Polomano Rosemary C.
Published: July 2022

Background:

Pennsylvania sudden unexpected infant death rates rank among the highest nationally. A nursing team developed, implemented, evaluated, and disseminated an evidence-based quality improvement (QI) program at birthing hospitals in Pennsylvania to address this issue. To facilitate implementation, clinical nurses were educated as Subject Matter Experts (SMEs) to empower them to transform and sustain outcomes-driven QI for infant safe sleep nursing practice.

Methods:

This descriptive study examined outcomes from 268 nurses who received comprehensive education on infant safe sleep and the SME role. Likert-type scale surveys measured knowledge gained and progress made in practice following education. A programmatic dashboard tracked program implementation. Descriptive statistics were used to report findings.

Intervention:

SME nurses (N = 268) completed two interactive learning modules addressing safe sleep guidelines and teaching strategies and attended a workshop to acquire skills for program implementation. Key competencies included data collection and dissemination, policy development, and communication techniques.

Results:

Immediate posteducation surveys completed by SMEs indicated that over 98% of respondents strongly agreed or agreed they were able to effectively demonstrate communication strategies, identify SME role components, provide environment surveillance, and demonstrate best practices in infant safe sleep. To allow time for assimilation of the of SME role, a survey was initiated at 6 months to capture progress made. Seventy-eight SMEs responded to the survey and reported exceptional or substantial progress in 10 areas for SME responsibilities.

Conclusion:

Use of the SME role for program implementation led to highly favorable SME-reported outcomes in leading a hospital-based QI program.
Pediatric Specialty Nursing Associations and their Role in Leadership Development
Authors: Beal Judy A.
Published: July 2022

Background:

Professional organizations have a long and rich history of promoting leadership development since the late 1800s. Professional nursing organizations and associations advocate for the profession of nursing and nurses, develop health care policies and standards that ensure the highest level of patient care quality, assure the highest level of education, provide professional development and continuing education, and offer research, networking, and career advancement opportunities for their members. Currently there are 10 nationally based pediatric nursing specialty organizations and associations, most of which also have regional or local chapters.

Purpose:

To use a scoping review to identify and summarize contributions of pediatric nursing organizations and associations in the United States to leadership development in pediatric nursing practice.

Results:

Although there are leadership programs sponsored by professional nursing organizations and mentions of leadership in their mission and “about us” statements, there is very little empirical evidence of the contributions that pediatric nursing specialty bodies make to the development of leaders.

Conclusions:

Membership in a professional nursing organization provides nurses with professional development; continuing education including journal subscription and conference attendance; networking; opportunities for specialty certification, career advancement, and leadership development; and research-based clinical standards and guidelines that promote best practice. The relationship between membership in pediatric professional organizations and leadership is clear in mission statements and strategic plans. Nurse leaders play a key role in advancing the organization's mission and goals. Nursing faculty, practice executives, and professional organizations and associations have an obligation to demonstrate value of membership in advancing the profession and developing future leaders. Future research is needed to describe the contributions of pediatric nursing professional organizations to leadership development of nurses.
AONL Foundation Innovates to Bridge Science and Practice
Authors: Joseph M. Lindell , Zimmermann Deborah , Begley Robyn , Ward Danielle
Published: July 2022

In this column, leaders from AONL discuss the AONL Foundation and its charitable mission of providing resources that create opportunities to bridge science and practice to shape the future of nursing.
A Crosswalk Analysis Between Magnet® Standards and Clinical Nurse Specialist Practice Competencies
Authors: Fulton Janet S. , Gilbert Jason H. , Rader Tiffany , Keen Alyson , Shay Amy C. , Moody Rachel , Walker Jane
Published: July 2022

OBJECTIVE

The purpose of this study was to determine the alignment between the American Nurses Credentialing Center's Magnet Recognition Program® standards and clinical nurse specialist (CNS) practice competencies.

BACKGROUND

Despite documentation of CNS contributions to achieving and sustaining Magnet Recognition®, there is a lack of evidence clearly aligning Magnet® standards and CNS practice competencies.

METHODS

Using a crosswalk method, an expert panel of CNSs and chief nursing executives analyzed alignment of the 50 Magnet standards with the 44 National Association of Clinical Nurse Specialists core practice competencies.

RESULTS

CNS practice competencies are aligned closely with Magnet standards: 86% of the 50 Magnet standards aligned with at least 1 CNS competency and 81.8% of CNS competencies aligned with at least 1 Magnet® standard.

CONCLUSIONS

The alignment between Magnet standards and CNS competencies supports evidence of CNS contributions to organizational achievement of Magnet Recognition and will assist nurse executives in identifying a full scope of opportunities for CNSs to contribute to nursing excellence.
Increasing Exposure to Primary Care Nursing Through Curriculum Revision and an Innovative Nursing Minor
Authors: Bell Tia , Blazek Julie , Elsea Karen , Morris Toni
Published: July 2022

Background:

The changing health care environment dictates a workforce competently trained to address chronic health care issues particularly in primary care settings. Curriculum analysis identified deficits in primary care education and the need to create academic opportunities that bridge the gap between primary health care needs and nursing preparation.

Method:

An existing academic-clinical partnership was leveraged to create a primary care minor for BSN students designed to provide a comprehensive adjunct to the traditional baccalaureate nursing curriculum. A total of 19 credits and 150 clinical hours are necessary to complete the minor. Additionally, the BSN curriculum was revised to include primary care for all students.

Results:

A total of 45 students and 26 preceptors have participated in the elective courses. Eight students have completed the minor with 11 additional students in the final course.

Conclusion:

A nursing curriculum with increased primary care exposure may improve workforce preparation and address health care needs.
Comorbid HIV Infection and Opioid Use Disorder Simulation for Nurse Practitioner Students
Authors: Woroch Ruth A. , Chu Minseung , Gingell Monica J.
Published: July 2022

Background:

Human immunodeficiency virus (HIV) infection and opioid use disorder (OUD) often occur as comorbid conditions. Many nurse practitioners are treating these conditions in their practice.

Problem:

Most advanced practice registered nursing (APRN) students do not encounter a medically complex patient with both HIV infection and OUD during their clinical experiences.

Approach:

We present an unfolding simulated standardized patient scenario involving both HIV infection and OUD for APRN students. During each of 3 semesters, the students encounter the patient as he presents for a sexually transmitted infection, an OUD relapse, and, finally, new-onset HIV infection. The scenarios become increasingly complex as the students progress in their clinical experiences.

Conclusion:

This innovative series of scenarios introduces APRN students to complex comorbid patient situations, with many issues to consider.
Cerebral Venous Thrombosis With Topical Estrogen-Progesterone Use in a Young Heterosexual Male
Authors: Aldraihem Moneera O. , Al-Senani Fahmi , Bashir Shahid
Published: July 2022

Introduction:

Our report sheds light on the risk of topical hormonal use in relation to cerebral venous sinus thrombosis. We diagnosed our patient with cerebral venous thrombosis (CVT) using computed tomography venogram, then detailed history and examination were obtained, and thorough blood tests and imaging were done to exclude other causes of CVT like thrombophilias, infections, and malignancies.

Case Report:

Our patient is a 37-year-old heterosexual male, presented with headache only. The computed tomography venogram showed extensive CVT in the right internal jugular vein, sigmoid, transverse, and straight cerebral venous; detailed history and investigations suggest that his use of crushed oral contraceptive pills mixed with water topically on the scalp is the most important predisposing factor. This patient was managed with anticoagulants and is being followed in the clinic.

Conclusion:

Oral hormonal use in contraceptives is a known risk factor for CVT. This case sheds light on the importance of topical hormonal use concerning CVT in females and males; it stresses the need for more studies in that area, as it is poorly studied.
Factors Associated With Drug Consumption Without Scientific Evidence in Patients With Mild COVID-19 in Peru
Authors: Soriano-Moreno David R. , Fernandez-Guzman Daniel , Sangster-Carrasco Lucero , Quispe-Vicuña Carlos , Grados-Espinoza Pamela , Ccami-Bernal Fabricio , Morocho-Alburqueque Noelia , Coba-Villan Naomi , Velasquez-Fernandez Randy , Nieto-Gutierrez Wendy
Published: July 2022

Objective

This study aimed to evaluate the factors associated with the consumption of drugs without scientific evidence in patients with mild COVID-19 infection in Peru.

Methods

An analytical cross-sectional study was carried out including 372 adult patients with a history of mild COVID-19 disease. Factors associated with drug consumption were evaluated by Poisson regressions with robust variance adjustment using the bootstrapping resampling method.

Results

Seventy-two percent consumed some medication without scientific evidence, with antibiotics (71%) and ivermectin for human use (68%) being the most commonly used. Factors associated with the consumption of drugs to treat mild COVID-19 infection were thinking that the drugs are not effective (adjusted prevalence ratio, 0.55; 95% confidence interval, 0.41–0.74) and not being informed about the efficacy of the drugs (adjusted prevalence ratio, 0.48; 95% confidence interval, 0.36–0.65).

Conclusions

Education of the population seems to be the main factor that increases the consumption of drugs without scientific evidence in the Peruvian population to treat mild COVID-19.
Inpatient Satisfaction With Surgical Resident Care After Elective General and Oncologic Surgery
Authors: McKinley Sophia K. , Wojcik Brandon M. , Witt Emily E. , Hamdi Isra , Mansur Arian , Petrusa Emil , Mullen John T. , Phitayakorn Roy
Published: July 2022

Objective:

To investigate inpatient satisfaction with surgical resident care.

Background:

Surgical trainees are often the primary providers of care to surgical inpatients, yet patient satisfaction with surgical resident care is not well characterized or routinely assessed.

Methods:

English-speaking, general surgery inpatients recovering from elective gastrointestinal and oncologic surgery were invited to complete a survey addressing their satisfaction with surgical resident care. Patients positively identified photos of surgical senior residents and interns before completing a modified version of the Consumer Assessment of Healthcare Providers and Systems Surgical Care Survey (S-CAHPS). Adapted S-CAHPS items were scored using the “top-box” method.

Results:

Ninety percent of recruited patients agreed to participate (324/359, mean age=62.2, 50.3% male). Patients were able to correctly identify their seniors and interns 85% and 83% of the time, respectively (P=0.14). On a 10-point scale, seniors had a mean rating of 9.23±1.27 and interns had a mean rating of 9.01±1.49 (P=0.14). Ninety-nine percent of patients agreed it was important to help in the education of future surgeons.

Conclusions:

Surgical inpatients were able to recognize their resident physicians with high frequency and rated resident care highly overall, suggesting that they may serve as a willing source of feedback regarding residents’ development of core competencies such as interpersonal skills, communication, professionalism, and patient care. Future work should investigate how to best incorporate patient evaluation of surgical resident care routinely into trainee assessment to support resident development.
Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network
Authors: Bres Capucine , Voron Thibault , Benhaim Leonor , Bergeat Damien , Parc Yann , Karoui Mehdi , Genser Laurent , Péré Guillaume , Demma Jonathan A. , Bacoeur-Ouzillou Ophélie , Lebreton Gil , Thereaux Jeremie , Gronnier Caroline , Dartigues Peggy , Svrcek Magali , Bouzillé Guillaume , Bardier Armelle , Brunac Anne C. , Roche Brigitte , Darcha Claude , Bazille Celine , Doucet Laurent , Belleannee Genevieve , Lejeune Sophie , Buisine Marie P. , Renaud Florence , Nuytens Frederiek , Benusiglio Patrick R. , Veziant Julie , Eveno Clarisse , Piessen Guillaume
Published: July 2022

Objective:

To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM).

Background:

Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative.

Methods:

A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression.

Results:

A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6–16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7–46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors (P=0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25).

Conclusions:

Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.
Sirtuin 1 deletion increases inflammation and mortality in sepsis
Authors: Labiner Hanna E. , Sas Kelli M. , Baur Joseph A. , Sims Carrie A.
Published: July 2022

BACKGROUND

Sepsis is a hyperinflammatory response to infection that can lead to multiorgan failure and eventually death. Often, the onset of multiorgan failure is heralded by renal dysfunction. Sirtuin 1 (SIRT1) promotes cellular stress resilience by inhibiting inflammation and promoting mitochondrial function. We hypothesize that SIRT1 plays an important role in limiting the inflammatory responses that drive organ failure in sepsis, predominantly via expression in myeloid cells.

METHODS

We performed cecal ligation and puncture (CLP) on whole body SIRT1 knockout (S1KO) and myeloid cell–specific S1KO (S1KO-LysMCre) mice on a C57BL/6J background. Serum interleukin (IL)-6 was quantified by enzyme-linked immunosorbent assay. Renal mitochondrial complex activity was measured using Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Blood urea nitrogen (BUN) was measured from serum. Survival was monitored for up to 5 days.

RESULTS

Following CLP, S1KO mice had decreased renal mitochondrial complex I–dependent respiratory capacity (241.7 vs. 418.3 mmolO2/mg/min, p = 0.018) and renal mitochondrial complex II–dependent respiratory capacity (932.3 vs. 1,178.4, p = 0.027), as well as reduced rates of fatty acid oxidation (187.3 vs. 250.3, p = 0.022). Sirtuin 1 knockout mice also had increased BUN (48.0 mg/dL vs. 16.0 mg/dL, p = 0.049). Interleukin-6 levels were elevated in S1KO mice (96.5 ng/mL vs. 45.6 ng/mL, p = 0.028) and S1KO-LysMCre mice (35.8 ng/mL vs. 24.5 ng/mL, p = 0.033) compared with controls 12 hours after surgery. Five-day survival in S1KO (33.3% vs. 83.3%, p = 0.025) and S1KO-LysMCre (60% vs. 100%, p = 0.049) mice was decreased compared with controls.

CONCLUSION

Sirtuin 1 deletion increases systemic inflammation in sepsis. Renal mitochondrial dysfunction, kidney injury, and mortality following CLP were all exacerbated by SIRT1 deletion. Similar effects on inflammation and survival were seen following myeloid cell–specific SIRT1 deletion, indicating that SIRT1 activity in myeloid cells may be a significant contributor for the protective effects of SIRT1 in sepsis.
The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes
Authors: Di Fonzo Alessio , Albanese Alberto , Jinnah Hyder A.
Published: July 2022

Purpose of review

We describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia.

Recent findings

The continuing discoveries of genetic causes for dystonia syndromes are transforming our view of these disorders. They share unexpectedly common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. The field has further expanded to include forms recently associated with endolysosomal dysfunction.

The discovery of biological pathways shared between different monogenic dystonias is an important conceptual advance in the understanding of the underlying mechanisms, with a significant impact on the pathophysiological understanding of clinical phenomenology. The functional relationship between dystonia genes could revolutionize current dystonia classification systems, classifying patients with different monogenic forms based on common pathways. The most promising effect of these advances is on future mechanism-based therapeutic approaches.
Recent advances in noninvasive brain stimulation for schizophrenia
Authors: Brunelin Jérôme , Adam Ondine , Mondino Marine
Published: July 2022

Purpose of review

Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms.

Recent findings

Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies.

Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.
Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review
Authors: van der Horst Marte Z. , Papadimitriou Georgia , Luykx Jurjen J.
Published: July 2022

Objective

Clozapine response varies widely from person to person, which may be due to inter-individual genetic variability. This umbrella review aims to summarize the current evidence on associations between pharmacodynamic genes and response to clozapine treatment.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology, a systematic literature search was conducted in the PubMed and EMBASE databases from inception to November 2021 to identify systematic reviews and meta-analyses of studies that examined genetic determinants of clozapine response. The quality of the reviews was assessed with the AMSTAR-2 tool.

Results

From a total of 128 records, 10 studies representing nine systematic reviews and one meta-analysis met our inclusion criteria. The overall quality of the included studies was poor. All systematic reviews concluded that the results of primary studies were largely negative or conflicting. Most evidence was found for an association with clozapine response and rs6313 and rs6314 within HTR2A and rs1062613 within HTR3A in the serotonergic system.

Conclusions

Conclusive evidence for associations between genetic variants and clozapine response is still lacking. Hypothesis-generating genetic studies in large, well-characterized study populations are urgently needed to obtain more consistent and clinically informative results. Future studies may also include multi-omics approaches to identify novel genetic determinants associated with clozapine response.
How do plankton species coexist in an apparently unstructured environment?
Authors: Kléparski Loïck , Beaugrand Grégory , Kirby Richard R.
Published: July 2022

In a paper entitled
The paradox of the plankton
, Hutchinson asked 'how it is possible for a number of species to coexist in a relatively isotropic or unstructured environment all competing for the same sorts of materials' (Hutchinson 1961
Am. Nat
.
95
, 137–145 (
doi:10.1086/282171
)). Particularly relevant for phytoplankton, this paradox was based on two implicit, and perhaps naive, postulates, i.e. (i) that all plankton species have similar requirements and (ii) that the marine environment is relatively homogeneous in space and time. A number of hypotheses, based on purely theoretical or experimental studies, have been proposed to solve this conundrum, ranging from spatio-temporal environmental heterogeneity to biotic chaotic variability. Here, we characterize the ecological niche of 117 plankton species belonging to three different taxonomic groups and show that all species have a niche sufficiently distinct to ensure coexistence in a structured marine environment. We also provide evidence that pelagic habitats are, unsurprisingly, more diverse in space and time than Hutchinson imagined, the marine environment being neither unstructured nor stable in space and time. We, therefore, conclude that the niche theory, and its corollary the principle of competitive exclusion, apply as much for the plankton as for other forms of life, be they terrestrial or marine.
Does mast seeding shape mating time in wild boar? A comparative study
Authors: Cachelou Jessica , Saint-Andrieux Christine , Baubet Eric , Nivois Eveline , Richard Emmanuelle , Gaillard Jean-Michel , Gamelon Marlène
Published: July 2022

In seasonal environments, the timing of reproduction often matches with the peak of food resources. One well-known effect of global warming is an earlier phenology of resources, leading to a possible mismatch between the timing of reproduction for consumers and food peak. However, global warming may also change the dynamics of food resources, such as the intensity and frequency of pulsed mast seeding. How quantitative changes in mast seeding influence the timing of reproduction of seed consumers remains unexplored. Here, we assess how yearly variation in mast seeding influences mating time in wild boar (Sus scrofa), a widespread seed consumer species. We took advantage of the intensive monitoring of both female reproduction (1636 females) and acorn production over 6 consecutive years across 15 populations of wild boar in the wild. We found that mating time occurs earlier when acorn production increases in most but not all populations. In two out of 15 populations, heavy females mated earlier than light ones. Our findings demonstrate that mast seeding advances the mating time in some populations, which could perhaps impact how boars respond to climate change.
An overlooked mechanism underlying the attenuated temperature response of soil heterotrophic respiration
Authors: Zhang Xiaoxian , Whalley Peter A. , Gregory Andrew S. , Whalley W. Richard , Coleman Kevin , Neal Andrew L. , Mooney Sacha J. , Soga Kenichi , Illangasekare Tissa H.
Published: July 2022

Biogeochemical reactions occurring in soil pore space underpin gaseous emissions measured at macroscopic scales but are difficult to quantify due to their complexity and heterogeneity. We develop a volumetric-average method to calculate aerobic respiration rates analytically from soil with microscopic soil structure represented explicitly. Soil water content in the model is the result of the volumetric-average of the microscopic processes, and it is nonlinearly coupled with temperature and other factors. Since many biogeochemical reactions are driven by oxygen (O
2
) which must overcome various resistances before reaching reactive microsites from the atmosphere, the volumetric-average results in negative feedback between temperature and soil respiration, with the magnitude of the feedback increasing with soil water content and substrate quality. Comparisons with various experiments show the model reproduces the variation of carbon dioxide emission from soils under different water content and temperature gradients, indicating that it captures the key microscopic processes underpinning soil respiration. We show that alongside thermal microbial adaptation, substrate heterogeneity and microbial turnover and carbon use efficiency, O
2
dissolution and diffusion in water associated with soil pore space is another key explanation for the attenuated temperature response of soil respiration and should be considered in developing soil organic carbon models.
Neophobia and innovation in Critically Endangered Bali myna,
Leucopsar rothschildi
Authors: Miller Rachael , Garcia-Pelegrin Elias , Danby Emily
Published: July 2022

Behavioural flexibility can impact on adaptability and survival, particularly in today's changing world, and encompasses associated components like neophobia, e.g. responses to novelty, and innovation, e.g. problem-solving. Bali myna (
Leucopsar rothschildi
) are a Critically Endangered endemic species, which are a focus of active conservation efforts, including reintroductions. Gathering behavioural data can aid in improving and developing conservation strategies, like pre-release training and individual selection for release. In 22 captive Bali myna, we tested neophobia (novel object, novel food, control conditions), innovation (bark, cup, lid conditions) and individual repeatability of latency responses in both experiments. We found effects of condition and presence of heterospecifics, including longer latencies to touch familiar food in presence than absence of novel items, and between problem-solving tasks, as well as in the presence of non-competing heterospecifics than competing heterospecifics. Age influenced neophobia, with adults showing longer latencies than juveniles. Individuals were repeatable in latency responses: (1) temporally in both experiments; (2) contextually within the innovation experiment and between experiments, as well as being consistent in approach order across experiments, suggesting stable behaviour traits. These findings are an important starting point for developing conservation behaviour related strategies in Bali myna and other similarly threatened species.
Neo-taphonomic analysis of the Misiam leopard lair from Olduvai Gorge (Tanzania): understanding leopard–hyena interactions in open settings
Authors: Domínguez-Rodrigo Manuel , Organista Elia , Baquedano Enrique , Cifuentes-Alcobendas Gabriel , Pizarro-Monzo Marcos , Vegara-Riquelme Marina , Gidna Agness , Uribelarrea David , Martín-Perea David
Published: July 2022

Misiam is a modern wildebeest-dominated accumulation situated in a steep ravine covered with dense vegetation at Olduvai Gorge (Tanzania). It is interpreted here as a leopard lair to which carcasses have been transported for several years. Felid-specific bone damage patterns, felid-typical skeletal part profiles, taxonomic specialization and the physical presence of leopards observed by the authors show that leopards at Misiam can be specialized medium-sized carcass accumulators. Hyenas also intervened at intervals in the modification of the retrieved faunal assemblage. This makes Misiam a carnivore palimpsest. Here, we additionally show that leopards only transport and accumulate carcasses on occasions, that they can seem highly specialized despite being dietary generalists, and that such a behaviour may be prompted by seasonal competition or during the breeding season or both. Misiam is the first open-air leopard lair with a dense bone accumulation reported. There, leopards engaged in intensive accumulation of carcasses during the wet season, when the southern Serengeti short-grass plains undergo the effect of the famous wildebeest migration and this migratory species reaches the gorge. The ecological importance of this behaviour and its relevance as a proxy for reconstructing prehistoric carnivore behaviours are discussed.
Ausichicrinites zelenskyyi
gen. et sp. nov., a first nearly complete feather star (Crinoidea) from the Upper Jurassic of Africa
Authors: Salamon Mariusz A. , Jain Sreepat , Brachaniec Tomasz , Duda Piotr , Płachno Bartosz J. , Gorzelak Przemysław
Published: July 2022

Fossil comatulids, referred to as feather stars, are mostly known from highly disarticulated specimens. A single isolated element (centrodorsal) has been the basis for taxonomic description of a vast majority of fossil comatulids. Here, we report a nearly complete, and thus extremely rare, comatulid from the Upper Jurassic (Tithonian) of the Blue Nile Basin in central western Ethiopia that provides a unique insight into the morphology of comatulid arms and cirri. It is assigned to
Ausichicrinites zelenskyyi
gen. et sp. nov. and is the first Jurassic comatulid from the African continent. The new taxon shows some similarities with representatives of the Mesozoic Solanocrinitidae but also has close resemblance with the modern family Zygometridae, exclusively known from the Holocene of western Pacific and eastern Indian Oceans. This morphologic similarity is considered to be due to convergence. The first example of pinnule regeneration in a fossil feather star is reported, which reinforces the hypothesis about the importance of predation in the evolution of these crinoids.
Errors of Interpretation - ‘Correcting the record on the comparative efficacy of surgical masks versus respirators: Historical research findings suggesting their equivalence and used to support downgraded respiratory protection for non-ICU UK healthcare workers, resulted from unrecognised errors of arithmetic’
Authors: Wilkinson Martyn AC , Curran Evonne T , Tomlinson David R
Published: July 2022

The first UK ‘COVID-19 Guidance for Infection Prevention and Control (IPC) in healthcare settings’, March 2020, restricted respiratory protection equipment (RPE) to aerosol generating procedures (AGPs) and the ICU. Supportive data in a linked meta-analysis stated equivalent protection – i.e., 80% - afforded by fluid resistant surgical face masks (FRSMs) and RPE, against SARS-CoV-1 infection.

Visual inspection of the meta-analysis data suggested greater healthcare worker (HCW) protection from RPE. Detailed statistical analysis confirmed significantly greater HCW protection from RPE (p<0.0009) compared to FRSMs: sadly, the meta-analysis had been subject to calculation error.

Research data supporting the restriction of RPE to AGPs and the ICU were flawed. Consequently, non-ICU HCWs have been inappropriately exposed to SARS-CoV-2 aerosol inhalation transmission.

To minimise HCW occupational COVID-19, UK IPC guidance should be changed to require RPE during all confirmed / suspected infectious SARS-CoV-2 patient care.
Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior
Authors: Brockway Dakota F. , Griffith Keith R. , Aloimonos Chloe M. , Clarity Thomas T. , Moyer J. Brody , Smith Grace C. , Dao Nigel C. , Hossain Md Shakhawat , Drew Patrick J. , Gordon Joshua A. , Kupferschmidt David A. , Crowley Nicole A.
Published: July 2022

Somatostatin (SST) neurons in the prelimbic (PL) cortex mediate a variety of behavioral states. However, little is known about the actions of somatostatin peptide signaling in shaping cortical functioning and behavior. Here, we sought to characterize the unique physiological and behavioral roles of the SST peptide in the PL cortex. We employed a combination ofex vivopharmacologic and optogenetic electrophysiology,in vivocalcium monitoring, andin vivopeptide pharmacology to explore the role of SST neuron and peptide signaling in the mouse PL cortex. Whole-cell slice electrophysiology was conducted in pyramidal and GABAergic neurons in the PL cortex of C57BL/6J and SST-IRES-Cre male and female mice to characterize the pharmacological mechanism of SST signaling. Fiber photometry of GCaMP6f fluorescent calcium signals from SST neurons was conducted to characterize the activity profile of SST neurons during exploration of an elevated plus maze (EPM) and open field test (OFT). We further used local delivery of both a broad SST receptor (SSTR) agonist and antagonist into bilateral PL cortex to test causal effects of SST administration and receptor blockade on these same exploratory behaviors. SSTR activation broadly hyperpolarized layer 2/3 pyramidal neurons in the PL cortex in both male and female miceex vivo, an effect that was recapitulated with optogenetic stimulation of SST neurons, through both monosynaptic and polysynaptic GABA neuron-mediated mechanisms of action. This hyperpolarization was blocked by pre-application of the SSTR antagonist cyclo-somatostatin (cyclo-SST) and was non-reversible. SST neurons in PL were activated during EPM and OFT exploration, indicating task-related recruitment of these neurons. Lastly, in line with this exploration-related activity profile, SSTR agonist administration directly into the PL enhanced open arm exploration in the EPM, whilein vivoadministration of an antagonist had no effect. Together, this work describes a broad ability for SST peptide signaling to modulate microcircuits within the prefrontal cortex and related exploratory behaviors.
MATEdb, a data repository of high-quality metazoan transcriptome assemblies to accelerate phylogenomic studies
Authors: Rosa Fernández , Vanina Tonzo , Carolina Simón Guerrero , Jesus Lozano-Fernandez , Gemma I. Martínez-Redondo , Pau Balart-García , Leandro Aristide , Klara Eleftheriadi , Carlos Vargas-Chávez
Published: July 2022

Abstract

With the advent of high throughput sequencing, the amount of genomic data available for animals (Metazoa) species has bloomed over the last decade, especially from transcriptomes due to lower sequencing costs and easier assembling process compared to genomes. Transcriptomic data sets have proven useful for phylogenomic studies, such as inference of phylogenetic interrelationships (e.g., species tree reconstruction) and comparative genomics analyses (e.g., gene repertoire evolutionary dynamics). However, these data sets are often analyzed following different analytical pipelines, particularly including different software versions, leading to potential methodological biases when analyzed jointly in a comparative framework. Moreover, these analyses are computationally expensive and not affordable for a large part of the scientific community. More importantly, assembled transcriptomes are usually not deposited in public databases. Furthermore, the quality of these data sets is hardly ever taken into consideration, potentially impacting subsequent analyses such as orthology and phylogenetic or gene repertoire evolution inference. To alleviate these issues, we present Metazoan Assemblies from Transcriptomic Ensembles (MATEdb), a curated database of 335 high-quality transcriptome assemblies from different animal phyla analyzed following the same pipeline. The repository is composed, for each species, of (1) a de novo transcriptome assembly, (2) its candidate coding regions within transcripts (both at the level of nucleotide and amino acid sequences), (3) the coding regions filtered using their contamination profile (i.e., only metazoan content), (4) the longest isoform of the amino acid candidate coding regions, (5) the gene content completeness score as assessed against the BUSCO database, and (6) an orthology-based gene annotation. We complement the repository with gene annotations from high-quality genomes, which are often not straightforward to obtain from individual sequencing projects, totalling 423 high-quality genomic and transcriptomic data sets. We invite the community to provide suggestions for new data sets and new annotation features to be included in subsequent versions, that will be analyzed following the same pipeline and be permanently stored in public repositories. We believe that MATEdb will accelerate research on animal phylogenomics while saving thousands of hours of computational work in a plea for open and collaborative science.
Multiset correlation and factor analysis enables exploration of multi-omic data
Authors: Brown Brielin C. , Wang Collin , Kasela Silva , Aguet François , Nachun Daniel C. , Taylor Kent D. , Tracy Russell P. , Durda Peter , Liu Yongmei , Johnson W. Craig , Van Den Berg David , Gupta Namrata , Gabriel Stacy , Smith Joshua D. , Gerzsten Robert , Clish Clary , Wong Quenna , Papanicolau George , Blackwell Thomas W. , Rotter Jerome I. , Rich Stephen S. , Ardlie Kristin G. , Knowles David A. , Lappalainen Tuuli
Published: July 2022

Multi-omics datasets are becoming more common, necessitating better integration methods to realize their revolutionary potential. Here, we introduce Multi-set Correlation and Factor Analysis, an unsupervised integration method that enables fast inference of shared and private factors in multi-modal data. Applied to 614 ancestry-diverse participant samples across five ‘omics types, MCFA infers a shared space that captures clinically relevant molecular processes.