bluuebunny/crossref_metadata_2025 huggingface dataset:
You Cannot Function in “Overwhelm”: Helping Primary Care Navigate the Slow End of the Pandemic
Authors: Sullivan Erin E. , Etz Rebecca S. , Gonzalez Martha M. , Deubel Jordyn , Reves Sarah R. , Stange Kurt C. , Hughes Lauren S. , Linzer Mark
Published: May 2024

Goal:

This study was developed to explicate underlying organizational factors contributing to the deterioration of primary care clinicians’ mental health during the COVID-19 pandemic.

Methods:

Using data from the Larry A. Green Center for the Advancement of Primary Health Care for the Public Good’s national survey of primary care clinicians from March 2020 to March 2022, a multidisciplinary team analyzed more than 11,150 open-ended comments. Phase 1 of the analysis happened in real-time as surveys were returned, using deductive and inductive coding. Phase 2 used grounded theory to identify emergent themes. Qualitative findings were triangulated with the survey’s quantitative data.

Principal Findings:

The clinicians shifted from feelings of anxiety and uncertainty at the start of the pandemic to isolation, lack of fulfillment, moral injury, and plans to leave the profession. The frequency with which they spoke of depression, burnout, and moral injury was striking. The contributors to this distress included crushing workloads, worsening staff shortages, and insufficient reimbursement. Consequences, both felt and anticipated, included fatigue and demoralization from the inability to manage escalating workloads. Survey findings identified responses that could alleviate the mental health crisis, namely: (1) measuring and customizing workloads based on work capacity; (2) quantifying resources needed to return to sufficient staffing levels; (3) promoting state and federal support for sustainable practice infrastructures with less administrative burden; and (4) creating patient visits of different lengths to rebuild relationships and trust and facilitate more accurate diagnoses.

Practical Applications:

Attention to clinicians’ mental health should be rapidly directed to on-demand, confidential mental health support so they can receive the care they need and not worry about any stigma or loss of license for accepting that help. Interventions that address work–life balance, workload, and resources can improve care, support retention of the critically important primary care workforce, and attract more trainees to primary care careers.
Supportive Care Needs of Patients With Temporary Ostomy in Enhanced Recovery After Surgery: A Mixed-Methods Study
Authors: HU Jieman , ZHANG Xiuling , SUN Jianan , HU Haiyan , TANG Chulei , BA Lei , XU Qin
Published: May 2024

Background

Enhanced recovery after surgery (ERAS), a global surgical quality improvement initiative, reduces the length of stay in the hospital. Temporary stoma care for rectal cancer is complex, and patients require prolonged care services to adjust to the stoma. The shorter stay durations in the new model challenge the conventional care pathways and create new patient needs.

Purpose

This study was designed to explore the supportive care needs of patients under the new surgical model to provide a reference for the design of ERAS nursing care plans.

Methods

A convergent parallel mixed-methods design was used in this study. Patients with temporary stomas for rectal cancer were recruited using a convenience sampling method in gastrointestinal surgery wards and wound & stoma clinics in two public tertiary care hospitals in China. Standardized questionnaires were administered to 140 patients to collect quantitative data, and semistructured interviews were conducted individually with 13 patients to collect qualitative data. The questionnaire data were analyzed using descriptive statistics, and the interview data were analyzed using thematic analysis.

Results

“Health system and information needs” and “care and support needs” were identified in both the qualitative and quantitative analyses as the most significant unmet needs of the participants. In addition, the qualitative analysis identified receiving focused stoma care instructions and easily understandable information as essential to fulfilling health system and information needs. Care and support needs included access to continued postdischarge services and attention from medical professionals.

Conclusion/Implications for Practice

The participants in this study experienced a variety of unmet supportive care needs under the ERAS protocol, with gaps particularly notable in two categories: “health system and information needs” and “care and support needs.” Increased perioperative care and shorter hospital stays under the ERAS protocol reduce opportunities for patients to receive targeted instruction and shift much of the ostomy education and care workload out of the hospital, requiring greater attention from clinical nurses to ensure quality of care.
Five Evidence-Based Strategies to Foster a Culture of Well-Being in Physician Assistant Education
Authors: Hoffmann Chelsey
Published: May 2024

Introduction

The objective of this study was to discuss evidence-based strategies to promote a culture of well-being with physician assistant (PA) education.

Methods

Published literature on medical student, resident, and PA student well-being was reviewed with findings subsequently categorized according to well-being strategy.

Results

Five themes were found from existing well-being research within medical student and PA student education: faculty role modeling and support, dedicated curricular time, pass/fail grading schema and de-emphasizing grades, peer support and learning communities, and evaluation importance.

Discussion

Physician assistant educators may be able to foster a culture of well-being for their students by making even small adjustments to the existing educational curriculum.
The Impact of Piezoelectric Device in Cholesteatoma Endoscopic Surgery: Retrospective Evaluation of Safety and Functional Results
Authors: Marchioni Daniele , Ronzani Guglielmo , Gazzini Sandra , Fulco Gianfranco , Rubini Alessia
Published: May 2024

Objective

Atticotomy represents an essential surgical step within the management of attical cholesteatoma during endoscopic ear surgery. The aim of the present study was to evaluate the safety and functional results of an endoscopic atticotomy performed with piezosurgery, in terms of audiological outcomes and tissue's healing.

Methods

This is an observational retrospective study on patients with attical cholesteatoma who underwent endoscopic ear surgery with piezoelectric atticotomy and subsequent scutum reconstruction either with tragal cartilage or temporalis muscle fascia. Scutumplasty's status was evaluated via scheduled outpatient controls through an endoscopic check and classified as stable or unstable at least 10 months after surgery. A pre- and postoperative audiometric examination was performed in each patient.

Results

Eighty-four patients were enrolled. In 50 out of 84 patients (59.52%), an exclusive endoscopic procedure was performed, whereas in 34 patients (40.48%) a combined microscopic/endoscopicapproach was adopted. In 72 cases (85.71%), scutum's reconstruction appeared to be normally positioned, whereas 12 patients developed a retraction pocket, which was self-cleaning in 8 of them and non–self-cleaning in the remaining 4. In 17 patients, a slight sensorineural hearing loss (between 5 and 15 dBHL) was observed, and in 2 patients, the loss was greater than 15 dBHL. Overall, no significative differences between pre- and postoperative pure-tone average bone thresholds resulted (p = 0.4983), though a mild significant hearing deterioration was detected by the specific analysis at 4000 Hz (p = 0.0291).

Conclusion

Piezosurgery represents an extremely useful tool in performing atticotomy during endoscopic tympanoplasties. Our data seem to support the safety of its usage in this specific step, as it did not lead to any significant sensorineural damage on overall pure-tone average. Moreover, satisfactory tissue healing in regard to scutum reconstruction was observed.
Stapedotomy Versus Cochlear Implantation for Far Advanced Otosclerosis: Insights From a Patient With Matched Preoperative and Postoperative Function
Authors: Khandalavala Karl R. , Dornhoffer Jim R. , Lane John I. , Carlson Matthew L.
Published: May 2024

Objective

To examine patient preference after stapedotomy versus cochlear implantation in a unique case of a patient with symmetrical profound mixed hearing loss and similar postoperative speech perception improvement.

Patients

An adult patient with bilateral symmetrical far advanced otosclerosis, with profound mixed hearing loss.

Intervention

Stapedotomy in the left ear, cochlear implantation in the right ear.

Main Outcome Measure

Performance on behavioral audiometry, and subjective report of hearing and intervention preference.

Results

A patient successfully underwent left stapedotomy and subsequent cochlear implantation on the right side, per patient preference. Preoperative audiometric characteristics were similar between ears (pure-tone average [PTA] [R: 114; L: 113 dB]; word recognition score [WRS]: 22%). Postprocedural audiometry demonstrated significant improvement after stapedotomy (PTA: 59 dB, WRS: 75%) and from cochlear implant (PTA: 20 dB, WRS: 60%). The patient subjectively reported a preference for the cochlear implant ear despite having substantial gains from stapedotomy. A nuanced discussion highlighting potentially overlooked benefits of cochlear implants in far advanced otosclerosis is conducted.

Conclusion

In comparison with stapedotomy and hearing aids, cochlear implantation generally permits greater access to sound among patients with far advanced otosclerosis. Though the cochlear implant literature mainly focuses on speech perception outcomes, an underappreciated benefit of cochlear implantation is the high likelihood of achieving “normal” sound levels across the audiogram.
Long-Term Outcomes of a Percutaneous Wide-Diameter Bone-Anchored Hearing Implant: A Clinical Evaluation of More than 800 Implants
Authors: Teunissen Emma M. , Caspers Coosje J.I. , Vijverberg Maarten A. , Pennings Ronald J.E. , Mylanus Emmanuel A.M. , Hol Myrthe K.S.
Published: May 2024

Objective

This study evaluates the clinical outcomes of 807 percutaneous wide-diameter bone-anchored hearing implants (BAHIs) in 701 patients. In addition, it compares patient groups and examines bone conduction device (BCD) usage.

Study design

Retrospective cohort study. Mean follow-up period of 3.8 years.

Setting

Tertiary referral center.

Patients

All patients implanted with a percutaneous wide-diameter BAHI until December 2020 were included. Patients were divided into age groups, “loading-time” groups, and, if applicable, specific subgroups thought to be at risk for complications postsurgery, e.g., intellectual disability and comorbidities.

Main outcome measures

Soft tissue reaction, implant survival, revision surgery, and BCD usage.

Results

In 9.1% of the 5,188 observations of 807 implants, an adverse soft tissue reaction was reported according to the Holgers’ scale. Significantly more (adverse) soft tissue reactions were observed in children and intellectually disabled (ID) patients (p < 0.05). Comorbidity subgroups showed no significant differences in soft tissue reactions. Implant loss percentage, including explantations, was 6.2%. Implant survival was significantly worse in patients with ID (14.1%; p = 0.021). Pediatric age, early loading, or comorbidities did not significantly influence implant survival. At least 592 implants (73.4%) were used for bone conduction hearing, of which 65.4% were used daily.

Conclusion

Both children and ID patients are more prone to (adverse) soft tissue reactions, ID patients only have a higher risk of implant loss. The rate of implant loss in children seemed to be reduced compared to previous studies and thus more comparable to adults since using wide-diameter implants.
Exploring the interconnected between type 2 diabetes mellitus and nonalcoholic fatty liver disease: Genetic correlation and Mendelian randomization analysis
Authors: Ni Wenjuan , Lu Yao , Wang Wei
Published: May 2024

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.
Research in revealing the effects on Cuscuta chinensis to diarrhea type irritable bowel syndrome based on network pharmacology and molecular docking potential mechanism
Authors: Yang Shili , Liu Huaiquan , Li Kewei , Chen Bo , Tang Yi , Li Jie , Wang Dan , Zhang Xinyan
Published: May 2024

To explore the potential mechanism inCuscuta sinensison diarrhea-type irritable bowel syndrome using network pharmacology and molecular docking techniques. First, the active components and related targets of Cuscuta were found setting oral utilization >30% and drug-like properties greater than or equal to 0.18 as filter information from TCMSP database. The targets of diarrheal irritable bowel syndrome were compiled by searching DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersections of drugs and targets related to the disease were taken for gene ontology enrichment and Kyoto encyclopedia of genes and genomes enrichment analyses, to elucidate the potential molecular mechanisms and pathway information ofCuscuta sinensisfor the treatment of diarrheal irritable bowel syndrome. The protein–protein interaction network was constructed by using the STRING database and visualized with Cytoscape_v3.10.0 software to find the protein–protein interaction network core At last, molecular docking was performed to validate the combination of active compounds with the core target. The target information of Cuscuta and diarrhea-type irritable bowel syndrome was compiled, which can be resulted in 11 active compounds such as quercetin, kaempferol, isorhamnetin, β-sitosterol, and another 17 core targets such as TP53, IL6, AKT1, IL1B, TNF, EGFR, etc, whose Kyoto encyclopedia of genes and genomes was enriched in the pathways of lipids and atherosclerosis, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, and fluid shear stress and atherosclerosis, etc. Docking demonstrated that the core targets and the active compounds were able to be better combined.Cuscuta chinensismay exert preventive effects on diarrhea-type irritable bowel syndrome by reducing intestinal inflammation, protecting intestinal mucosa, and playing an important role in antioxidant response through multi-targets and multi-pathways.
Revisiting resistant hypertension in kidney disease
Authors: Bansal Shweta
Published: May 2024

Purpose of review

As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined.

Recent findings

Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD.

This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.
Machine perfusion in liver transplantation: recent advances and coming challenges
Authors: Wehrle Chase J. , Jiao Chunbao , Sun Keyue , Zhang Mingyi , Fairchild Robert L. , Miller Charles , Hashimoto Koji , Schlegel Andrea
Published: May 2024

Purpose of review

Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field.

Recent findings

Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its’ protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.

The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging.

Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.
Exploring Holistic Cancer Care and Survivorship in India Through the Kerala Model of Palliative Care
Authors: George Prema Naittee , Ganesh M. P.
Published: May 2024

Support groups and meetings are self-help gatherings that provide a unique sense of community, unconditional acceptance, and information on cancer and its treatment. This cross-sectional study examined 12 outpatient meetings within the Kerala model of palliative care, a community-based service provided to patients irrespective of disease, stage, or prognosis starting from the time of diagnosis. The study focused on the pivotal role of community nurses in facilitating these meetings, with participants including cancer patients and survivors. Using in-depth interviews (n = 52) and participant observations, this research used a qualitative approach and explored the dynamics and outcomes of outpatient meetings. Findings highlight the indispensable contributions of these community nurses serving as linchpins in providing support, guiding discussions, and offering crucial education. Outpatient meetings effectively addressed psychosocial concerns, combatted stigmas associated with cancer, and promoted informed decision making in cancer care. The study emphasizes the need for recognizing the role played by community nurses in improving psychosocial support and diminishing stigma, and ultimately the quality of life of patients and survivors through the palliative cancer care within the Kerala model. We also underscore the need for policy initiatives, resource allocation, and training programs tailored to support these frontline health care providers effectively.
High-Frequency Heart Rate Variability Is Prospectively Associated With Sleep Complaints in a Healthy Working Cohort
Authors: Cribbet Matthew R. , Thayer Julian F. , Jarczok Marc N. , Fischer Joachim E.
Published: May 2024

Objective

Vagus nerve functioning, as indexed by high-frequency heart rate variability (HF-HRV), has been implicated in a wide range of mental and physical health conditions, including sleep complaints. This study aimed to test associations between HF-HRV measured during sleep (sleep HF-HRV) and subjective sleep complaints 4 years later.

Methods

One hundred forty-three healthy employees (91% male; MAge = 47.8 years [time 2], SD = 8.3 years) of an industrial company in Southern Germany completed the Jenkins Sleep Problems Scale, participated in a voluntary health assessment, and were given a 24-hour ambulatory heart rate recording device in 2007. Employees returned for a health assessment and completed the Jenkins Sleep Problems Scale 4 years later.

Results

Hierarchical regression analyses showed that lower sleep HF-HRV measured in 2007 was associated with higher self-reported sleep complaints 4 years later after controlling for covariates (r
ab,c = −0.096, b = −0.108, 95% CI, −0.298 to 0.081, ΔR
2 = 0.009, p = .050).

Conclusions

These data are the first to show that lower sleep HF-HRV predicted worse sleep 4 years later, highlighting the importance of vagus nerve functioning in adaptability and health.
Making a Statement
Authors: LaValley Myles N. , Eble Danielle J. , Kuzon William M. , Peters Blair R. , Skokan Alexander J. , Ettinger Russell E. , Morrison Shane D.
Published: May 2024

Objective:

Despite politically charged media coverage and legislation surrounding gender-affirming care (GAC), many organizations have released position statements to provide scientifically backed clinical practice standards, combat misinformation, and inform medicolegal policies. The purpose of this study is to objectively assess the availability and the content of the official position statements of relevant medical professional organizations regarding GAC.

Summary Background Data:

A list of US medical professional organizations with likely involvement in GAC based on medical or surgical specialties was compiled.

Methods:

For included organizations, we evaluated the availability, content, and publication year of positions on GAC through October 2023. When available, formal positions were categorized as supportive or unsupportive.

Results:

A total of 314 professional medical organizations were screened for our study based on specialty, relevance to GAC, and issuance of patient guidelines or position statements. Inclusion criteria were met by 55 organizations. Most organizations (35, 63.6%) had formal position statements on GAC. Support for GAC was described in 97.1% (n=34). Further, 94.2% (n=33) of available statements explicitly addressed GAC in individuals less than 18 years old and were largely supportive (96.9%, n=32).

Conclusions:

This cross-sectional analysis demonstrates that a majority of multidisciplinary professional medical organizations with relevance to GAC have issued formal position statements on the topic. Available positions were overwhelmingly supportive of individualized access to gender-affirming therapies in adult and adolescent populations. However, silence from some organizations continues to represent a modifiable disparity in the provision of GAC.
Examining the Frequency of Second Endoscopy and Its Effect on Patient Outcomes With Upper Gastrointestinal Bleeding in Southeast of Iran
Authors: Alijani Fatemeh , Khoshnazar Seyedeh Mahdieh , Eslami Omid
Published: May 2024

Background:

This study investigated the frequency and impact of repeat endoscopy in patients with acute upper gastrointestinal bleeding (AUGIB) in a referral hospital in Southeast Iran.

Materials and Methods:

A cross-sectional descriptive-analytical study was conducted on the records of 190 patients who underwent endoscopy for AUGIB in 2019. The study compared the demographic and clinical characteristics, outcomes, and treatments of patients who had a second endoscopy (n=64) with those who did not (n=126). The data were analyzed with SPSS software, and aPvalue less than 0.05 was considered significant.

Results:

The results showed that repeat endoscopy was not significantly associated with age, gender, initial symptoms, bleeding site, first endoscopy time, or disease outcome. However, repeat endoscopy was significantly associated with higher bleeding severity, different wound types, different bleeding causes, longer hospital stay, and different treatments in the first endoscopy. The main reasons for repeat endoscopy were poor visibility and recurrent bleeding. The majority of repeat endoscopies were performed within 2 days of the first one. Most patients who had a second endoscopy did not receive any treatment, and those who did received combined thermal and epinephrine injections.

Conclusions:

The study concluded that routine second endoscopy is not necessary for all patients with AUGIB, but it may be beneficial for some cases. Further research is needed to clarify the indications and timing of repeat endoscopy in AUGIB.
Aspergillus esophagitis in a patient with solid tumors: a case report
Authors: Abi Rached Vanessa , Azar Karine , Gerges Sarah , Hallit Souheil , Akoury Elie , Chahine Georges , Hallit Rabih , Akiki Bassem , Rizk Rita
Published: May 2024

Esophageal aspergillosis is a rare occurrence primarily documented in hematologic malignancies, and only rarely occurring among patients with solid tumors. In this case report, we present the unique case of an 81-year-old Lebanese man who had a remarkable medical history, including four solid tumors. The patient sought medical attention due to dysphagia and weight loss, prompting a gastroscopic examination that revealed a necrotic abscess at the esophagogastric junction. Initial treatment with fluconazole and Proton Pump Inhibitors was administered, but the recurrence of similar symptoms led to a repeat gastroscopy, unveiling a diagnosis of Aspergillus esophagitis. Intravenous Voriconazole was promptly initiated; however, the patient developed a significant pericardial effusion and expired, with Aspergillus species identified in the pericardial fluid. This exceptional case emphasizes the importance of considering esophageal aspergillosis in cancer patients who present with refractory symptoms such as epigastric pain, dysphagia, nausea, and vomiting, despite symptomatic treatment. Our findings underscore the need for increased awareness and the inclusion of gastrointestinal endoscopy as part of the diagnostic approach for this rare but potentially life-threatening condition.
Clostridium tanneri sp. nov., isolated from the faecal material of an alpaca
Authors: Miller Samuel , Hendry Meredith , King Jacobey , Sankaranarayanan Krithivasan , Lawson Paul A.
Published: May 2024

A strictly anaerobic, Gram-stain-negative rod-shaped bacterium, designated A1-XYC3T, was isolated from the faeces of an alpaca (Lama pacos). On the basis of the results of a comparative 16S rRNA gene sequence analysis, the isolate was assigned to the genus Clostridium with the highest sequence similarities to Clostridium magnum DSM 2767T (96.8 %), Clostridium carboxidivorans P7T (96.3 %) and Clostridium aciditolerans JW/YJL-B3T (96.1 %). The average nucleotide identity between A1-XYC3T, C. magnum, C. carboxidivorans and C. aciditolerans was 77.4, 76.1 and 76.6  %, respectively. The predominant components of the cellular fatty acids of A1-XYC3T were C14 : 0, C16 : 0 and summed feature 10, containing C18:0/C17:0 cyclo. The DNA G+C content was 32.4 mol%. On the basis of biochemical, phylogenetic, genotypic and chemotaxonomic criteria, this isolate represents a novel species within Clostridium sensu stricto for which the name Clostridium tanneri sp. nov. is proposed. The type strain of this species is strain A1-XYC3T (=CCM 9376T=NRRL B-65691T).
Guide assignment in single-cell CRISPR screens using crispat
Authors: Braunger Jana M. , Velten Britta
Published: May 2024

Motivation

Pooled single cell CRISPR screens have emerged as a powerful tool in functional genomics to probe the effect of genetic interventions at scale. A crucial step in the analysis of the resulting data is the assignment of cells to gRNAs corresponding to a specific genetic intervention. However, this step is challenging due to a lack of systematic benchmarks and accessible software to apply and compare different guide assignment strategies. To address this, we here propose crispat (CRISPR guide assignment tool), a Python package to facilitate the choice of a suitable guide assignment strategy for single cell CRISPR screens.

Results

We demonstrate the package on four single cell CRISPR interference screens at low multiplicity of infection from two studies, where crispat identifies strong differences in the number of assigned cells, downregulation of the target genes and number of discoveries across different guide assignment strategies, highlighting the need for a suitable guide assignment strategy to obtain optimal power in single cell CRISPR screens.

Availability and Implementation

crispat is implemented in python and the source code, installation instructions and tutorials can be found athttps://github.com/velten-group/crispat. Code to reproduce all findings in this paper is available athttps://github.com/velten-group/crispat_analysis.

Contact

Britta Velten,britta.velten@cos.uni-heidelberg.de

Supplementary Information

Supplementary Information can be found in the Supplementary Information file.
Morphotype-specific calcium signaling in human microglia
Authors: Nevelchuk Sofia , Brawek Bianca , Schwarz Niklas , Valiente-Gabioud Ariel , Wuttke Thomas V. , Kovalchuk Yury , Koch Henner , Höllig Anke , Steiner Frederik , Figarella Katherine , Griesbeck Oliver , Garaschuk Olga
Published: May 2024

Key functions of Ca2+signaling in rodent microglia include monitoring the brain state or the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca2+dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca2+signal properties of human microglia remain unknown. Using a newly developed toolbox, we analyzedin situCa2+signaling of decades-old human cortical microglia. The data revealed marked compartmentalization of Ca2+signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca2+levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca2+signaling, the fraction and the amplitude of process Ca2+signals and the duration of somatic Ca2+signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca2+signals and the duration of process Ca2+signals increased along this pathway.
Plastic responses to past environments shape adaptation to novel selection pressures
Authors: Coates Sarah E. R. , Comeault Aaron A. , Wood Daniel P. , Fay Michael F. , Creer Simon , Osborne Owen G. , Dunning Luke T , Papadopulos Alexander S. T.
Published: May 2024

Phenotypic plasticity may pave the way for rapid adaptation to newly encountered environments. Although it is often contested, there is growing evidence that initial plastic responses of ancestral populations to new environmental cues may promote subsequent adaptation. However, we do not know whether plasticity to cues present in the ancestral habitat (past-cue plasticity) can facilitate adaptation to novel cues. Conceivably, this could occur if plastic responses are coincidentally optimal to both past and novel cues (i.e., are pre-adaptive) or if they are transferred to novel cues during adaptation. Past plastic phenotype values could also become fixed and genetically co-opted during adaptation to the new environment. To uncover the role of past-cue plasticity in adaptation, we tested gene expression plasticity responses of two parallel mine-waste adaptedSilene uniflorapopulations and their closest coastal relatives. Plants were exposed to the past and novel-cues of salt and zinc, which revealed that during adaptation to mine-waste plasticity to salt diminishes. Despite this, our results show that ancestral plasticity to salt has a substantial impact on subsequent adaptation to zinc. For a third of genes that have evolved zinc plasticity in mine populations, salt plasticity has been transferred to the zinc response. Furthermore, a quarter of fixed expression differences between mine and coastal populations were similar to ancestral salt responses. Alongside evidence that ancestral plasticity to novel cues can facilitate adaptation, our results provide a clear indication that ancestral past-cue plasticity can also play a key role in rapid, parallel adaptation to novel habitats.

Significance Statement

The role of phenotypic plasticity in promoting adaptation is hotly debated, with conflicting evidence for the benefits of ancestral plasticity in newly encountered environments. Here, we present an alternative mode by which ancestral plasticity can promote adaptation. We investigated whether phenotypic plasticity towards environmental cues that are experienced only in ancestral habitats (past-cue plasticity) can significantly contribute towards rapid adaptation to completely distinct cues. We show that, in the maritime plant species,Silene uniflora, past-cue plasticity to salt has made a substantial contribution to rapid adaptation to heavy-metal pollution in newly encountered habitats. This phenomenon has broad implications for the capacity and predictability of species to persist in the face of anthropogenic environmental change.
Phasing millions of samples achieves near perfect accuracy, enabling parent-of-origin classification of variants
Authors: Williams Cole M. , O’Connell Jared , Freyman William A. ,   23andMe Research Team, Gignoux Christopher R. , Ramachandran Sohini , Williams Amy L.
Published: May 2024

Haplotype phasing, the process of determining which genetic variants are physically located on the same chromosome, is crucial for various genetic analyses. In this study, we first benchmark SHAPEIT and Beagle, two state-of-the-art phasing methods, on two large datasets: > 8 million diverse, research-consented 23andMe, Inc. customers and the UK Biobank (UKB). We find that both perform exceptionally well. Beagle’s median switch error rate (SER) (after excluding single SNP switches) in white British trios from UKB is 0.026% compared to 0.00% for European ancestry 23andMe research participants; 55.6% of European ancestry 23andMe research participants have zero non-single SNP switches, compared to 42.4% of white British trios. South Asian ancestry 23andMe research participants have the highest median SER amongst the 23andMe populations, but it is still remarkably low at 0.46%. We also investigate the relationship between identity-by-descent (IBD) and SER, finding that switch errors tend to occur in regions of little or no IBD segment coverage.

SHAPEIT and Beagle excel at ‘intra-chromosomal’ phasing, but lack the ability to phase across chromosomes, motivating us to develop an inter-chromosomal phasing method, called HAPTIC (HAPlotypeTIling andClustering), that assigns paternal and maternal variants discretely genome-wide. Our approach uses identity-by-descent (IBD) segments to phase blocks of variants on different chromosomes. HAPTIC represents the segments a focal individual shares with their relatives as nodes in a signed graph and performs bipartite clustering on the signed graph using spectral clustering. We test HAPTIC on 1022 UKB trios, yielding a median phase error of 0.08% in regions covered by IBD segments (33.5% of sites). We also ran HAPTIC in the 23andMe database and found a median phase error rate (the rate of mismatching alleles between the inferred and true phase) of 0.92% in Europeans (93.8% of sites) and 0.09% in admixed Africans (92.7% of sites). HAPTIC’s precision depends heavily on data from relatives, so will increase as datasets grow larger and more diverse. HAPTIC enables analyses that require the parent-of-origin of variants, such as association studies and ancestry inference of untyped parents.
Intratumoral administration of mRNA-1273 vaccine delays melanoma growth in mice
Authors: Boehm Dylan T. , Landreth Kaitlyn M. , Kilic Emel Sen , Lee Katherine S. , Misra Bishal , Bobbala Sharan , Heath Damron F. , Liu Tracy W.
Published: May 2024

Background

Immunotherapies are advantageous for treating cancers; however, their efficacy is limited in unresponsive hosts with “cold” tumor microenvironments. This limitation primarily stems from the lack of infiltrating CD8+T cells, which are major effectors of the anti-cancer immune response. Here, we demonstrate the effects of intratumoral (IT) injections of the COVID-19 mRNA vaccine on the impairment of tumor growth in mice.

Methods

Established B16F10 subcutaneous tumor models in wild type mice were used to evaluate the tumor response from IT administration of mRNA-1273. We compared treatment outcomes, immune composition, and transcriptomic effects from mRNA-1273 using survival studies, intravital imaging, flow cytometry, single-cell RNA sequencing, and abscopal studies. The ability of mRNA-1273 to enhance immune checkpoint therapy response was also evaluated.

Results

Tumor growth and survival studies following a single IT injection of the COVID-19 mRNA-1273 vaccine showed significant tumor suppression and prolonged survival in tumor-bearing mice. mRNA-1273 treatment resulted in a significant increase in CD8+T cell infiltration into the tumor microenvironment, as observed using intravital imaging and flow cytometry. Further tumor growth suppression was achieved using additional mRNA-1273 treatments. Combination administration of mRNA-1273 with immune checkpoint therapies demonstrated enhanced effects, further delaying tumor growth and improving the survival time of tumor-bearing mice.

Conclusion

IT injection of mRNA-1273 significantly reduced tumor growth and enhanced CD8+T cells in the tumor microenvironment. Tumor suppression was further enhanced following multiple injections of mRNA-1273 or when combined with immune checkpoint therapies. This study demonstrates that mRNA vaccines may be used as adjuvants for immunotherapies.

What is already known on this topic

Most cancer patients develop adequate antibody response to vaccination with mRNA-1273 and produce spike-specific T cell responses. However, it is unclear if the mRNA-1273 vaccine can be used to elicit anti-tumor T cell responses.

What this study adds

Intratumoral injection of mRNA-1273 significantly delayed melanoma growth.

Treatment with mRNA-1273 significantly increased CD8+T cell infiltration into the tumor microenvironment.

Enhanced effects of combination mRNA-1273 and immune checkpoint therapy in anti-tumor immunity.

How this study might affect research, practice, or policy

mRNA vaccine may be an effective adjuvant with immune checkpoint therapy.
Triphasic Thrombosis Model: A Computational Study of Type B Aortic Dissection
Authors: Gupta Ishan , Schanz Martin , Ricken Tim
Published: May 2024

Thrombosis refers to the formation of a thrombus, or a blood clot, within the body, which can occur either partially or completely. It serves as a crucial indicator of the severity of a patient’s medical condition, with the location and characteristics of thrombosis dictating its clinical implications. Hence, accurate diagnosis and effective management of thrombosis are paramount.

In our current investigation, we incorporate the porous attributes of a thrombus using the Theory of Porous Media. This involves dividing the aggregate into solid, liquid, and nutrient phases and utilising volume fractions to capture microstructural details. Fluid flow through the porous media is modelled using a modified Darcy-Brinkman type equation, with interaction terms within balance equations facilitating the modelling of the mass exchange and other phase interactions. The shorter time scales are neglected.

We present a comprehensive framework of equations and assumptions governing the behaviour of a strongly coupled multiphasic porous medium problem. Additionally, we introduce scenarios involving type B Aortic Dissection and false lumen geometries, providing a detailed outline of the problem setup. Thereafter, we present the potential of the model for thrombi growth. The simulation results are compared with velocity plots aligning with Magnetic Resonance Imaging data for three distinct cases with varying entry and exit tear sizes. Consequently, our proposed model offers a promising and reasonable approach for numerically simulating thrombosis and gaining insights into the underlying growth mechanics.
Generating intermediate slices with U-nets in craniofacial CT images
Authors: Nishimoto Soh , Kawai Kenichiro , Nakajima Koyo , Ishise Hisako , Kakibuchi Masao
Published: May 2024

Aim

The Computer Tomography (CT) imaging equipment varies across facilities, leading to inconsistent image conditions. This poses challenges for deep learning analysis using collected CT images. To standardize the shape of the matrix, the creation of intermediate slice images with the same width is necessary. This study aimed to generate inter-slice images from two existing CT images.

Materials and Methods

The study utilized CT images from the Japanese Facial Bone Fracture CT Collection Project. The pixel values were converted to Hounsfield numbers and normalized. Three re-slice systems utilizing U-nets were developed: 1/3, 1/4, and 1/5. The datasets were divided into training and validation sets, and data augmentation techniques were applied. The U-net models were trained for 200 epochs. Validation was conducted using validation datasets. The generated images were compared to the corresponding original images using peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and mean squared error (MSE) calculations. Results: Statistical analysis revealed significant differences between linear interpolation and U-net prediction in all indexes.

Conclusion

The developed re-slice systems with U-net models showed practical value for making intermediate slice images from the existing images in the craniofacial area.
Executive Resources Shape the Effects of Language Predictability Across the Adult Lifespan
Authors: Schuckart Merle , Martin Sandra , Tune Sarah , Schmitt Lea-Maria , Hartwigsen Gesa , Obleser Jonas
Published: May 2024

Humans predict upcoming language effortlessly, but the cognitive costs of these predictions remain debated. In this study, we demonstrate that limiting executive resources through a concurrent task reduces the effect of language predictability on reading times. Participants (N=175, replication N=96) read short articles presented word-by-word while completing a secondary font colour n-back task, thus varying cognitive demand. Language predictability was indexed by word surprisal as derived from a generative pre-trained transformer model (GPT-2). Our results show that predictability effects increase with age (18–85 years), and across both samples, higher cognitive load consistently diminished the impact of word predictability on reading speed. These findings highlight the resource-dependent nature of predictive mechanisms in language comprehension across the lifespan. We conclude that linguistic predictions rely on executive resources, which helps resolve the debate about the cognitive cost of predictive language processing.
Spatial modulation of facial expression: enhanced recognition of faces behind the observer
Authors: Tamura Hideki , Kobayashi Yugo , Nakauchi Shigeki , Minami Tetsuto
Published: May 2024

Our ability to recognize facial expressions is crucial for understanding others’ emotions1and facilitating smooth communication2. Numerous studies have explored how we perceive these cues, considering factors such as health3, social signals4and personality traits5. However, most of this research involves observers facing a monitor and assessing facial stimuli presented directly in front of them. Real-life scenarios offer more diverse spatial dynamics, such as conversing with someone at a table or glancing back at a passerby. Thus, faces behind the observer might trigger heightened recognition, akin to reacting swiftly to a perceived threat. Herein, we demonstrate that facial expression recognition is influenced by spatial relationships, i.e., faces in front of versus behind the observer. Participants judged the expressions of faces appearing in front of or behind them in virtual space. The findings of three experiments reveal an enhanced level of recognition for faces behind the participant. Interestingly, this effect varies with emotional valence; anger is amplified merely by the presence of a face behind the observer, while happiness requires actively turning to the rear for enhancement to occur. These findings suggest a biological instinct for perceiving threats behind us, potentially influencing subsequent actions. Hence, spatial relationships may modulate facial expression recognition.
Nothing but lies: improving the validity of neural predictors of deception
Authors: Lee Sangil , Niu Runxuan , Zhu Lusha , Kayser Andrew , Hsu Ming
Published: May 2024

Deception is a universal human behavior. Yet longstanding skepticism about the validity of measures used to understand the biological mechanisms underlying deceptive behavior has relegated such studies to the scientific periphery. Here we address these fundamental questions by applying novel machine learning methods and functional neuroimaging to signaling games capturing motivated deception in human participants. First, we develop an approach to test for the presence of confounding processes and thereby validate past skepticism by showing that much of the predictive power of neural predictors trained on deception data comes from confounding processes. Second, we show that the presence of confounding signals need not be fatal, and we improve the validity of our neural predictor via a novel machine learning procedure that identifies and removes these confounding signals. Together, these findings point to a scientific approach for studying a neglected class of behavior, with important methodological and societal implications.