bluuebunny/crossref_metadata_2025 huggingface dataset:
A bidirectional cohort study to compare the outcomes of transperitoneal and retroperitoneal approaches in subjects undergoing laparoscopic live donor nephrectomy
Authors: S. Praveena , Krishnamoorthy Venkatesh , Tyagaraj Krishnaprasad
Published: September 2023

Background

Laparoscopic transperitoneal donor nephrectomy (LDN) is currently the standard procedure for renal donation from living donors. Only a handful of clinical studies have compared the outcomes of retroperitoneoscopic donor nephrectomy (RLDN) and LDN. More robust data and systematic comparative analyses of the outcomes and complications of these 2 techniques are needed. This study aimed to elucidate the noninferiority of RLDN to LDN.

Materials and methods

All live renal donors who underwent either RLDN or LDN at our institution during the period of January 2015 to March 2021 were considered subjects, excluding those who refused to participate in the study. This was a bidirectional cohort study. Demographic and clinical data were collected and analyzed using standard statistical methods. Statistical significance was set atp< 0.05.

Results

Our study included 89 subjects: 40 in the LDN group and 49 in the RLDN group. The RLDN group had significantly shorter warm ischemia time (2.85 vs. 6.04 minutes), a lower fall in hemoglobin on postoperative day (POD)-1 (1.73 vs. 2.24 g/dL), lower estimated blood loss (601.93 vs. 797.27 mL), and lower pain on POD-1 (0.78 vs. 1.28). The improvement in recipient’s estimated glomerular filtration rate on POD-30 was significantly higher in the RLDN group (79.98 vs. 63.73 mL/min/1.73 m2). There was a significantly higher fall in estimated glomerular filtration rate of donor after nephrectomy in RLDN group on POD-30 (35.53 vs. 30.60 mL/min/1.73 m2). However, there were no significant differences in other parameters.

Conclusions

Our study, conducted in India, showed that the majority of RLDN outcomes were better than those of LDN. Hence, RLDN is clearly non-inferior to the gold standard LDN. A well-designed randomized controlled study is required to elucidate the statistical superiority of one approach over another.
“Weight loss is my goal and being healthy is my goal… I can get over the hot flashes”: a qualitative exploration of menopausal transition experiences and preferences for weight management among White women
Authors: Kracht Chelsea L. , St. Romain Jessica , Hardee Julie C. , Santoro Nanette , Redman Leanne M. , Marlatt Kara L.
Published: September 2023

Objectives

A qualitative research study design was used to (1) describe experiences of White women during the menopausal transition, and (2) identify barriers and facilitators for participating in a lifestyle program targeting weight management.

Methods

Perimenopausal and postmenopausal White women who self-reported a desire to lose or maintain weight participated in focus groups. Women were queried about their past diet, exercise, and weight management practices; menopausal transition; and specific components and considerations for developing a lifestyle program for weight management. Thematic analysis was conducted on coded transcripts and four main themes emerged, each containing three to six subthemes.

Results

Twenty-eight White women (age 54 ± 3 y, body mass index 31.4 ± 9.5 kg/m2) were enrolled. Overall, women felt menopause was a major life event that coincided with weight gain and frustrating body changes. Women already engaged in many different types of exercises and diets to lose weight. Women also talked to healthcare professionals about menopause but were disappointed in the support they received. Women were interested in a lifestyle program that included menopause-specific education, which focused on results beyond weight, which was flexible to their busy lifestyle, and which provided opportunities to build camaraderie among other women experiencing menopause.

Conclusions

This cohort of White women were interested in receiving menopause information and improving their overall health as part of a lifestyle program targeting weight management during this transition. Building camaraderie with other women affected by menopause is important to women, as is creating a lifestyle program that is flexible with daily life.
Potential Role of Smartphone Technology in Advancing Work on Neurological Soft Signs with a Focus on Schizophrenia
Authors: Gray Lucy E. , Buchanan Robert W. , Keshavan Matcheri S. , Torous John
Published: September 2023

Learning Objective: After participating in this CME activity, the psychiatrist should be better able to

• Outline and Identify potential benefits of using neurological soft signs (NSS) as biomarkers of schizophrenia.

Since the late 1960s, NSS have been a focus of study across psychiatric illnesses, including depression, bipolar disorder, and schizophrenia in particular. Utilizing these subtle neurological impairments as biomarkers of illness has numerous benefits; NSS offer a direct connection between clinical presentation and neurological functioning, and assessments are cost-effective. However, incongruent measurement scales, confounding variables, and rating system subjectivity have hindered the advancement and scalability of NSS research and clinical implementation. This article provides a brief overview of the literature on NSS as related to schizophrenia, and proposes utilizing smartphone sensing technology to create standardized NSS assessments with objective scoring. Incorporating digital phenotyping into NSS assessment offers the potential to make measurement more scalable, accessible, and directly comparable across locations, cultures, and demographics. We conducted a narrative search in PubMed and APA PsycInfo using the following keywords: neurological soft signs, schizophrenia spectrum disorders, and psychotic illnesses. No date limitations were used. There is no other direct work on NSS and new smartphone methods like digital phenotyping; though, there is related work in neurology. Harnessing advances in smartphone technology could provide greater insight into and further our understanding of specific aspects of the NSS field. For instance, it could help us distinguish trait vs. state markers and better understand how distinct groups of signs may reflect different aspects of psychiatric illness and neurological impairment. In addition, such technology can help advance research on the capabilities of NSS as an effective diagnostic tool.
Persistent Localized Descemet Membrane Endothelial Keratoplasty Detachments Secondary to Corneal Ink Stain Marks
Authors: Patel Radhika Pooja , Price Liam , Bizrah Mukhtar , Din Nizar
Published: September 2023

Purpose:

The aim of this study was to describe 2 cases of persistent endothelial graft detachments secondary to corneal gentian violet ink stain marks.

Methods:

This study included a case review of hospital records of 2 eyes with localized Descemet's membrane detachments after Descemet membrane endothelial keratoplasty (DMEK) surgery.

Results:

Two patients underwent consecutive uncomplicated DMEK surgery for Fuchs endothelial dystrophy with identical techniques. The grafts were marked with an ink marker through a stromal window to ensure correct orientation during donor graft preparation. Both patients had localized detachments around the ink mark on day 1, week 1, and up to 1 month at postoperative review. The persistent detachment was believed to be due to the gentian violet marker used which had a higher concentration of isopropyl alcohol solvent than the standard marking pen routinely used.

Conclusions:

Ink markers with higher concentrations of isopropyl solvent may result in higher DMEK detachment rates and caution is advised when using these markers.
Survey on Changes in the Willingness to Receive the COVID-19 Vaccine Among Patients with Breast Cancer in the Postpandemic Era
Authors: Bai Lixiao , Li Jianbin , Yang Ailing , Ding Cuicui , Li Jiayi , Wang Yan , Li Liangying , Zhang Shaohua , Jiang Zefei
Published: September 2023

This study aimed to investigate the status of and changes in the vaccination willingness of patients with breast cancer to increase the coronavirus disease 2019 (COVID-19) vaccination rate among these patients. The first survey included patients from the Fifth Medical Center of the PLA General Hospital who participated in the Society of Clinical Oncology Breast Cancer Committee NCP-02 study conducted from September 16 to December 31, 2021. The second survey was conducted from December 9 to December 26, 2022, for those who had not received vaccines previously. In total, 266 patients completed two questionnaires. A total of 143 patients (53.8%) changed their willingness to receive the vaccination. Among them, 45, who were initially unwilling to be vaccinated, changed their stance to become hesitant and 15 changed to become willing. Among those with hesitant attitudes toward vaccines, 45 changed their stance to become willing, and 28 changed to become unwilling; 10 patients with willing attitudes toward vaccines changed to become hesitant. Those who received surgery (odds ratio (OR), 4.24; 95% confidence interval (CI), 1.45–12.42; P = 0.01) and who lived with older adults or children (OR, 2.03; 95% CI, 1.13–3.62; P = 0.02) were more likely to change their attitudes toward COVID-19 vaccines. This finding suggested that patients with breast cancer were cautious about receiving the COVID-19 vaccine. Multiple methods should be used to promote vaccination and reduce vaccine hesitancy.
The Quest for Understanding Cutaneous Leishmaniasis in Northern Province, Sri Lanka: An Analysis of Clinical Data From the District General Hospital, Vavuniya
Authors: Arulenthiran Rajadurai , Murugananthan Arumugam , Amarasinghe Kanchana P. , Mathivathani Umashankar
Published: September 2023

The study aimed to examine the clinical and epidemiological patterns of cutaneous leishmaniasis (CL) in patients attending the Dermatology Unit, District General Hospital in Vavuniya, Sri Lanka. A total of 77 patients clinically suspected for CL were interviewed through a structured questionnaire, and skin-lesion samples were obtained between January 2016 and January 2017. The definitive diagnosis of CL was made through microscopic identification of smears, histopathological examination of biopsies and kDNA PCR. Treatment modalities were chosen based on the location of the lesions on the body and complexity of the lesions. Of 77 suspected patients, 68 were confirmed for CL, with a mean age of 34.6 (±12.7) years, and included 54 males (79.4%) and 14 females (20.6%). Being a male was a significant risk factor (P = 0.032, OR = 4.82) associated with CL. Lesions were observed mainly on the exposed areas of the body, of which the forearm (22.1%) was the most commonly affected site. Single lesions (75.0%) and ulcerated nodules with central crust (39.7%) were the prominent features among the infected group. The age group of 21–40 years was significantly associated with healing lesions (P = 0.028, marginal effect = 0.55). However, a significant negative relationship was detected between ulcerated nodular lesions and lesion healing (P = 0.0436, marginal effect = −0.375). Males are at higher risk of CL. Early diagnosis and specific treatment, along with preventive measures such as protective clothing and sand fly repellents, can limit the spread of the disease. There is a need for a comprehensive approach to prevent and control the transmission of CL.
Increasing Knowledge in the Requesting of Clinical Investigations
Authors: Guest Brogan , Donaldson-Perrott Amy , Hickman Beck , Louis Chandran , Ritsema Tamara , Roberts Karen
Published: September 2023

Purpose

Overtesting, ordering diagnostic investigations that do not help diagnose or manage a patient, is well-recognized as a problem across multiple healthcare settings in developed countries. One of the reasons often cited for overtesting is a lack of confidence or knowledge, so this article addresses our attempt to reduce overtesting through an investigation-specific course for a physician associate (PA) program based in the United Kingdom. We found no evidence of pedagogical literature that focused on clinical diagnostics teaching and assessment for PAs, so we aim to be the first to provide this research.

Methods

To assess student confidence, student feedback was collected through open-ended focus groups and qualitative surveys. The effectiveness of the course was evaluated through students' scores on investigation single best answer assessments.

Results

Overall, qualitative feedback from students showed an increase in knowledge in accurate investigation requests and interpretation. Students' assessment scores show a marked improvement after the implementation of the course.

Conclusion

This approach to an investigation-specific course, with a focus on limiting overinvestigating, demonstrates improved student performance on investigation assessments at the university level.
Physician Assistant Faculty Perceptions Regarding Ongoing Self-assessment and Accreditation
Authors: Kulo Violet , Cawley James F. , Fleming Shani , Gordes Karen L. , Jun Hyun-Jin , Kayingo Gerald
Published: September 2023

Purpose

While the processes of ongoing self-assessment and accreditation provide significant benefits to physician assistant (PA) programs, faculty members are often challenged by the required procedures and standards set by accreditation agencies. This study explored faculty perspectives regarding the processes of ongoing self-assessment and accreditation in PA programs.

Methods

A qualitative research design centered around semistructured interviews was used. A total of 26 participants were recruited, including PA program directors, associate program directors, directors of assessment and accreditation, past Accreditation Review Commission on Education for the Physician Assistant commissioners, accreditation consultants, deans, and PA Education Association leaders.

Data Collection

Semistructured one-on-one interviews were conducted by 8 members of the research team through Zoom video conferencing. Data were collected until saturation was reached.

Data Analysis

The interview recordings were transcribed and analyzed independently by 3 researchers. The transcripts were imported into NVivo, a qualitative data analysis software, for coding and inductive thematic analysis.

Results

Six emergent themes were identified under 2 major categories: facilitators and challenges. Facilitators for conducting continuous programmatic review and analysis include it takes a village, internal and external support, and sustained faculty development, whereas challenges are lack of knowledge and time, unclear expectations, and inflexibility.

Conclusion

The study highlights factors associated with facilitating the ongoing self-assessment process. However, a number of challenges were also identified. The study suggests opportunities for intervention at the program, institution, and profession level.
Caring for Appalachians With Intravenous Drug Use–Associated Infective Endocarditis at End of Life
Authors: Todt Kendrea
Published: September 2023

The purpose of this study was to describe the experiences of nurses caring for patients with intravenous drug use–associated infective endocarditis at the end of life in Appalachia. This study was a secondary analysis of 9 phenomenological unstructured interviews conducted by the author with nurses as part of a study exploring their lived experiences caring for this population. Data were analyzed using van Manen's 6-step approach. The analysis revealed 5 themes: (1) care at the end of life as a resolve to care for lost causes, (2) care at the end of life as an act of courageous communication, (3) care at the end of life as a resolve to endure chaos, (4) care at the end of life as a resolve to protect self and others, and (5) care at the end of life as a resolve to carry on and let go. Nurses perceived patients who use injection drugs as being at the end of life with eventual death. Patients with recurrent infective endocarditis from drug use are viewed as lost causes. To empower nurses, they need to be at the table of surgical decision making. Communication being one of a nurse's greatest tools, end-of-life communication education is needed. Administrative support should be a standard to safeguard nurses when dealing with emotionally challenging situations.
Demystifying Limited Code
Authors: Sabolish Rachel , Pennartz Lauren
Published: September 2023

Upon admission to an acute care hospital, patients and families are faced with determining their cardiopulmonary resuscitation status during conversation with providers. Medical providers are tasked with providing education and options in the context of the patient's acute and chronic conditions. Misconceptions are common in the general public, and providers may struggle with providing guidance in high-stress situations. Literature review revealed a lack of national consensus on code status definitions. Electronic health records may include multiple options for code status orders, which may lead to confusion for patients and medical staff, resulting in provision of potentially ineffective or undesired medical care. The following discussion will examine multiple cases in a large health care system and a novel way of standardizing resuscitation options using Havelock's change theory. This quality improvement project was approved by the institutional review board.
Retrospective Evaluation of Mycoplasma genitalium Prevalence and Macrolide Resistance in a Study Cohort of Pregnant Women in Birmingham, AL, From 1997 to 2001
Authors: Totten Arthur H. , Xiao Li , Van Der Pol Barbara , Szychowski Jeff , Subramaniam Akila , Geisler William M.
Published: September 2023

In a prospective study conducted in 2020 to 2021, macrolide resistance–associated mutations were found in 41% of pregnant persons in Birmingham, AL, with Mycoplasma genitalium detected. We retrospectively evaluated M. genitalium in 203 pregnant persons participating in a study conducted in 1997 to 2001 in Birmingham and adjacent areas and found a prevalence of 11% (95% confidence interval, 6.9%–15.7%), but no macrolide resistance–associated mutations.
CRP Versus SAA for Identification of Inflammatory Hepatic Adenomas
Authors: Soon Gwyneth S.T. , Yasir Saba , Jain Dhanpat , Kakar Sanjay , Wu Tsung-Teh , Yeh Matthew M. , Torbenson Michael S. , Chen Zongming Eric
Published: September 2023

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P-value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score (P<0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score (P<0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.
Advancing Face Transplantation: A Critical Analysis of Revisions and Long-Term Surgical Outcomes in 10 Cases
Authors: Mookerjee Vikram G. , Kauke-Navarro Martin , Hauc Sacha C. , Huelsboemer Lioba , Formica Richard N. , Pomahac Bohdan
Published: September 2023

Background:

Face transplantation has emerged as a viable solution for reconstructing the most complex facial injuries. Previous work has demonstrated that surgical revisions are necessary to optimize outcomes. The authors’ group has updated the previous report of revisions in their cohort, quantified and described which revisions were performed for functional, aesthetic, or mixed indications, and described the rationale, safety, and long-term outcomes of these revisions.

Methods:

A retrospective analysis of the authors’ 10 face transplants from April of 2009 to February of 2023 was performed. The patients’ medical records, preoperative facial defects, and operative reports (index and secondary revisions) were reviewed.

Results:

Nine patients were included. One patient underwent irreversible acute-on-chronic allograft rejection and received a second face transplant. The average number of revisions was 5.2 per patient (range, 2 to 11 procedures). The median time interval from transplantation to first revision was 4 months (range, 1 to 21 months). Median follow-up was 106 months (range, 39 to 142 months). Most interventions consisted of debulking the allograft or revising the periorbital tissues.

Conclusions:

In the current study, the authors report longer-term data on revision procedures needed in face transplant recipients. Patients should expect to undergo revisions for both functional and aesthetic considerations. Although the majority of revisions are performed within 2 years after transplantation, revisions can be safely performed at any time point. Shared decision-making between the patient and provider team is essential in deciding which revisions are performed and when.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
American Association for the Surgery of Trauma/American College of Surgeons Committee on Trauma: Clinical protocol for damage-control resuscitation for the adult trauma patient
Authors: LaGrone Lacey N. , Stein Deborah , Cribari Christopher , Kaups Krista , Harris Charles , Miller Anna N. , Smith Brian , Dutton Richard , Bulger Eileen , Napolitano Lena M.
Published: September 2023

Damage-control resuscitation in the care of critically injured trauma patients aims to limit blood loss and prevent and treat coagulopathy by combining early definitive hemorrhage control, hypotensive resuscitation, and early and balanced use of blood products (hemostatic resuscitation) and the use of other hemostatic agents. This clinical protocol has been developed to provide evidence-based recommendations for optimal damage-control resuscitation in the care of trauma patients with hemorrhage.
John Frank Allen. 6 May 1908—22 April 2001
Authors: G. M. Armitage Jonathan , Longair CBE FRS Malcolm S.
Published: September 2023

John Frank (Jack) Allen was a Canadian-born pioneer of low temperature physics. With his graduate student, Don Misener, he discovered the phenomenon of superfluidity on passing HeII through very narrow glass capillaries. Simultaneously, and independently, the phenomenon was discovered by Piotr Kapitza FRS in the Soviet Union. Jack's most famous discovery in 1938 was the fountain effect in liquid HeII, a further manifestation of the role of superfluidity at very low temperatures. The Nobel Prize for the discovery of superfluidity was awarded to Kapitza in 1978. Jack invented the O-ring as a reliable vacuum seal and, in 1947, followed this by the indium-ring cryogenic seal. In 1958, with John Bardeen (ForMemRS 1973) and Jan de Boer, he initiated a project that saved three million cubic feet of helium gas from being lost to the world. After running the Mond Laboratory in the Cavendish Laboratory from the late 1930s, in 1947 he was appointed professor of natural philosophy at St Andrews University, where he led the construction of a new physics building and built up an internationally respected department. He campaigned for student representation, and was well known for his physics demonstrations. In later life, he carried out a programme to erect plaques to Nevil Maskelyne FRS, who measured the gravitational constant
G
, and to celebrate the achievements of St Andrews luminaries.
Gamification as a tool to teach key concepts in microbiology to bachelor students in biology: a case-study using microbial interactions and soil functioning
Authors: Estoppey Aislinn , Tinguely Camille , Cravero Melissa , Blandenier Estelle , Brand Lucie , Court Julien , Zaninetti Marie , Bindschedler Saskia , Junier Pilar
Published: September 2023

Microbiology is a difficult topic to teach given that the objects of study are for the most invisible to the learner. The majority of university students starting their training in biology are more interested in natural objects that can be seen with the naked eye. Nonetheless, microorganisms are key components of the biosphere and a good microbiological background is required for a thorough training in natural sciences. Lecturing is still a common teaching format at the university. However, it is a passive learning format that is no longer considered the most adequate approach in most teaching situations. Instead, alternatives consisting in more active teaching formats have been recognized to better motivate students to acquire and consolidate knowledge. In addition, other transferable skills such as effective communication, critical thinking, and time management, are acquired simultaneously. A similar engagement can be obtained using games as part of the teaching experience. In this study, we designed a card game to teach key concepts in basic bacteriology and mycology to bachelor level students. The first task consistent in creating and designing microbial characters based on a list of species. This proved very useful for second-year bachelor students to learn concepts such as cell morphologies, taxonomy, and life cycles. In the second task, third-year students used the characters created in the second-year class to develop a game based on an ecological function, forest litter degradation. In addition, they also considered experimental validation of the microbial activities and incorporated knowledge acquired in other fields.
Sperm competition influences sperm quality and seminal plasma protein expression among territorial males of the courtship cichlid
Authors: Morita Masaya , Satoh Shun , Ito Takeshi , Kohda Masanori , Awata Satoshi
Published: September 2023

Sperm competition drives the plasticity of sperm quality and seminal fluid. However, how environmental and behavioral factors influence sperm competition and its outcome on the plasticity of sperm quality are unknown. In this study, we show males can asses the sperm competition level, and their fertilization-promoting sperm traits changes according to intensity. The promiscuous Tanganyikan cichlidsOphthalmotilapia ventralisperform their fertilization in the female mouth cavity. Sperm competition occurs in the female mouth as sperm is collected from multiple males. Behavioral (i.e., courtship success rates [CSR]) and environmental (density of spawning sites [DS]) factors are related to sperm collection. Seminal plasma glycoprotein 120 (SPP120) aids in sperm immobilization and aggregation, and sperm quality (longevity and velocity) could increase the probability of siring offspring. Based on an assumption of the involvement of DS and CSR on sperm collection, DS and CSR could influence the expression of SPP120 and sperm quality. We examined how sperm quality and SPP120 affect sperm competition-associated CSR and DS. Sperm longevity and velocity were positively correlated with DS. SPP120 expression was also positively correlated with CSR and DS. The plasticity of sperm quality and amount of SPP120 result in high fertilization competency according to sperm competition level.
Population-specific effects of ocean acidification in the Olympia oyster
Authors: Spencer Laura H , Silliman Katherine , Roberts Steven
Published: September 2023

Populations of marine species that respond differently to ocean acidification offer natural reservoirs of biodiversity that can be leveraged for conservation efforts and to sustain marine food systems. The molecular and physiological traits associated with tolerance to acidification must first be identified. This study leveraged oysters from three phenotypically distinct populations of the Olympia oyster,Ostrea lurida, but that were bred and reared in common conditions for four years. We assessed their growth, reproductive development, and transcriptional response to acidification within and across generations. Responses reveal energetic trade-offs that reflect unique physiotypes previously observed among populations. The population with the slowest growth but high survival rates, oysters from Dabob Bay, mounted the largest transcriptional response to acidification without effects to growth and reproduction. A moderate response was observed in the population with fastest growth rate but lowest fecundity (Fidalgo Bay). Oyster Bay, the population with highest fecundity but lowest survival rates, did not respond at the transcript level. Oyster Bay was also the only population for which acidification negatively affected growth and reproductive development. While exposure to acidification did not affect gene expression in the next generation’s larval stage, it did result in larger larvae in the Oyster Bay population, which could partially alleviate negative effects of acidification in the wild for that population. Given the distinct transcriptional response of the Dabob Bay population to acidification and its high survival rates in previous studies, we then identified genes that were uniquely expressed in Dabob Bay oysters compared to the other populations. Genes involved in antibacterial and antiviral processes, metabolism, growth, and reproduction were uniquely expressed in Dabob Bay, and many similar functions were identified in both adults and larvae, which provides insight into the mechanisms behind a stress-tolerant oyster population. The population-specific physiotypes and responses to acidification illustrate the diversity of physiological strategies inO. luridathat balance the energetic demands of growth, reproduction, cellular maintenance, and offspring viability. Taken together this study reveals that there are distinct physiotypes among marine invertebrate populations on small geographic scales with implications for species resilience to acidification and other environmental stressors.
Highly localized chemical sampling at sub-second temporal resolution enabled with a silicon nanodialysis platform at exceedingly slow flows
Authors: Park Insu , Kim Sungho , Brenden Christopher Kenji , Shi Weihua , Iyer Hrishikesh , Bashir Rashid , Vlasov Yurii
Published: September 2023

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and in pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100μm spatial resolution and sub-second temporal resolution at high recovery rates. These performance metrics, which are 100X-1000X superior to existing MD approaches, are enabled by a 100X reduction of the microfluidic channel cross-section, a corresponding drastic 100X reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with unprecedented spatio-temporal resolution for clinical, biomedical, and pharmaceutical applications.
Longevity interventions in Titan mice attenuate frailty and senescence accumulation
Authors: Gille Benedikt , Müller-Eigner Annika , Gottschalk Shari , Wytrwat Erika , Langhammer Martina , Peleg Shahaf
Published: September 2023

Wild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and cellular senescence at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at early age increases the lifespan and reduces cellular senescence. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.
Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires
Authors: Braun Jasper , Hill Elliot D. , Contreras Elisa , Yasuda Michie , Morgan Alexandra , Ditelberg Sarah , Winter Ethan , Callahan Cody , Mazzoni Gabrielle , Kirmaier Andrea , Mirebrahim Hamid , Asgharian Hosseinali , Telman Dilduz , Collier Ai-Ris Y. , Barouch Dan H. , Riedel Stefan , Dutta Sanjucta , Rubelt Florian , Arnaout Ramy
Published: September 2023

Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B– and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects’ SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRβ (TRB), and TCRδ (TRD) genes in parallel from all subjects, including select B– and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects’ electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination, but not infection, has a substantial effect on non-productively recombined IGHs, suggesting a vaccine effect that precedes clonal selection. We found that repertoires’ binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned fuzzy matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B– and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.
Transcriptional modulation during photomorphogenesis in rice seedlings
Authors: Gupta Parul , Jaiswal Pankaj
Published: September 2023

Light is one of the most important factors regulating plant gene expression patterns, metabolism, physiology, growth, and development. To explore how light may induce or alter transcript splicing, we conducted RNA-Seq-based transcriptome analyses by comparing the samples harvested as etiolated seedlings grown under continuous dark conditions vs. the light-treated green seedlings. We identified 14,766 differentially expressed genes, of which 4369 genes showed alternative splicing. We observed that genes mapped to the plastid-localized methyl-erythritol-phosphate (MEP) pathway were light-upregulated compared to the cytosolic mevalonate (MVA) pathway genes. Many of these genes also undergo splicing. These pathways provide crucial metabolite precursors for the biosynthesis of secondary metabolic compounds needed for chloroplast biogenesis, the establishment of successful photosynthetic apparatus, and photomorphogenesis. In the chromosome-wide survey of the light-induced transcriptome, we observed intron retention as the most predominant splicing event. In addition, we identified 1709 novel lncRNA transcripts in our transcriptome data.
γδ T cells respond directly and selectively to the skin commensal yeastMalasseziafor IL-17-dependent fungal control
Authors: Ruchti Fiorella , Tuor Meret , Mathew Liya , McCarthy Neil E , LeibundGut-Landmann Salomé
Published: September 2023

Stable microbial colonization of the skin depends on tight control by the host immune system. The lipid-dependent yeastMalasseziatypically colonizes skin as a harmless commensal and is subject to host type 17 immunosurveillance, but this fungus has also been associated with diverse skin pathologies in both humans and animals. Using a murine model ofMalasseziaexposure, we show that Vγ4+dermal γδ T cells expand rapidly and are the major source of IL-17A mediating fungal control in colonized skin. A pool of memory-likeMalassezia-responsive Vγ4+T cells persisted in the skin, were enriched in draining lymph nodes even after fungal clearance, and were protective upon fungal re-exposure up to several weeks later. Induction of γδT17 immunity depended on IL-23 and IL-1 family cytokine signalling, whereas Toll-like and C-type lectin receptors were dispensable. Furthermore, Vγ4+T cells fromMalassezia-exposed hosts were able to respond directly and selectively toMalassezia-derived ligands, independently of antigen-presenting host cells. Reactivity of human γδ T cells againstMalasseziaspp. confirmed the relevance of this fungus-specific response across different host species. The fungal moieties detected were shared across diverse species of theMalasseziagenus, but not conserved in other Basidiomycota or Ascomycota. These data provide novel mechanistic insight into the induction and maintenance of type 17 immunosurveillance of skin commensal colonization that has significant implications for cutaneous health.

AUTHOR SUMMARY

Malasseziais the most abundant fungus living on our skin and is usually harmless, but this microbe has also been shown to play a role in pathological conditions such as eczema and dermatitis. Here, we investigated how a population of Vγ4+γδ T cells protect mouse skin against fungal overgrowth. While generally considered part of the innate immune system, we found that γδ T cells were maintained long afterMalasseziawas cleared from the skin of experimentally-infected animals. These cells displayed memory-like features and were highly efficient at fighting the fungus after a secondary challenge. We observed that classic fungal pattern recognition receptors were not involved, and that antigen-presenting cells were not required to generateMalassezia-protective γδ T cells. Finally, we confirmed that γδ T cells can recogniseMalassezia, both in mice and human hosts. The fungal structure that triggers these responses was highly specific toMalasseziaand was not conserved among other fungi. Our results highlight for the first time an important role for γδ T cells in preventing uncontrolled growth of the most abundant skin fungus. These findings have implications for severalMalassezia-associated pathologies including eczema, dermatitis, and potentially even cancer.
No single PCR test is sufficient to determine parvovirus IHHNV presence in or impact on farmed shrimp production
Authors: Sritunyalucksana Kallaya , Sanguanrut Piyachat , Srisala Jiraporn , Thawonsuwan Jumroensri , Saleetid Nattakan , Vanichviriyakit Rapeepun , Chotwiwatthanakun Charoonroj , Flegel Timothy W. , Taengchaiyaphum Suparat
Published: September 2023

The main purpose of this report is to provide hard evidence that the shrimp parvovirus IHHNV has not resulted “in significant consequences e.g. production losses, morbidity or mortality at a zone or country level” in Thailand since at least 2010. It also reveals that no single PCR test is sufficient to identify IHHNV-infected shrimp. It presents historical evidence and new evidence from 11 commercial ponds cultivating the giant tiger shrimpPenaeus monodonin Thailand. These ponds were selected because they were the ponds that gave positive PCR test results for IHHNV using 2 methods recommended for IHHNV diagnosis by WOAH. However, an additional in-house “IHHNV Long-Amp method” (IHHNV-LA) was also used to amplify 90% of the 4 kb IHHNV genome sequence, and it also gave false-positive test results with 2 of the 11 ponds. Further tests using normal histopathological analysis for the presence of pathognomonic Cowdry A type inclusions (CAI),in situhybridization (ISH) and immunohistochemistry (IHC) could confirm IHHNV infections in only 2 of the 4 ponds PCR-positive using all 3 PCR methods. In addition, positive detection of CAI alone was equivalent to ISH or IHC in confirming IHHNV infection after a positive test with any of the PCR methods used. In summary, the recommended WOAH PCR methods gave false positive test results for IHHNV infection with 9/11 ponds (82%). All 11 ponds gave profitable harvests despite the confirmation of IHHNV in 2 ponds, where it was accompanied by various additional pathogens. Unfortunately, according to current practice, positive PCR test results with the WOAH methods alone sometimes leads to rejection of traded shrimp products without assurance that the test results are not false positive results that may arise from endogenous viral elements (EVE).
Bet hedging in a unicellular microalga
Authors: Tang Si , Liu Yaqing , Hammerschmidt Katrin , Zhu Jianming , Cheng Xueyu , Liu Lu , Zhou Jin , Cai Zhonghua
Published: September 2023

Abstract

Understanding how organisms adapt to unpredictable future environments is a fundamental goal in biology, which becomes even more urgent in an era of rapid climate change. One evolutionary adaptation to randomly fluctuating environments is bet hedging, a strategy that successfully facilitates reproduction and population persistence and has been widely reported from microbes to humans. Empirical evidence for its presence in microalga, one of Earth’s most important primary producers and carbon sinks, is lacking. Here, we report a bet-hedging strategy in the unicellular microalgaHaematococcus pluvialis.In a series of experiments, we show that an isogenicH. pluvialispopulation reversibly diversifies into hetero-phenotypic mobile and non-mobile subunits, independent of environmental conditions. Mobile cells grow faster but are more susceptible to external stressors, while non-mobile cells hardly grow but are more stress-resistant. This is attributed to dramatic shifts from growth-promoting activities (cell division, photosynthesis) to resilience-promoting cellular metabolic processes, including cell enlargement and aggregation, and accumulation of antioxidant and energy-storaging compounds. Our results provide experimental evidence for bet hedging in microalga, which has implications for their potential to adapt to current and predicted future conditions, and thus for the conservation of ecosystem functions.
Development and Characterization of Co-crystals Assisted withIn-silicoScreening for Solubility and Permeability Enhancement of Curcumin
Authors: Singh Meera , Takawale Shweta , Patil Rajesh , Chaudhari Somdatta , Pathan Aarifkhan , Sangshetti Jaiprakash , Moin Abu Tayab , Zubair Talha , Uddin Mohammad Helal
Published: September 2023

Despite being a promising phytochemical, Curcumin’s potential applications are limited due to its classification in BCS class IV, which is associated with low water solubility and permeability. Enhancing the bioavailability of BCS class IV drugs presents a significant challenge, but crystal chemistry provides a hopeful avenue for overcoming this hurdle. In this research, co-crystals of Curcumin were developed to improve both solubility and permeability. Unlike traditional methods that require extensive trial-based lab work and time-consuming screening of co-formers, the use of molecular docking inIn-silicoco-former screening offers a scientific and rational approach to selecting suitable partners. In this study, two distinct co-crystals were synthesized using a solvent evaporation technique with methanol as the solvent, employing a 1:1 molar ratio. L-proline and piperine were chosen as co-formers to enhance solubility and permeability, respectively. The co-crystals underwent optimization and characterization through Design of Experiments (DOE). Comparing the dissolution study results for the same curcumin concentration, the cumulative drug release (CDR) after 8 hours was 20% for pure curcumin and an impressive 71% for curcumin-L-proline co-crystals. The permeability study, conducted over four hours using the everted gut sac method in phosphate buffer pH 6.8, revealed curcumin’s permeability to be less than 0.05 mg/mL, while curcumin-piperine co-crystals exhibited a five-fold increase (0.2545 mg/mL) in permeability. The co-crystals formed through a molecular ratio of 1:1 for curcumin-L-proline to enhance solubility and 1:1 for curcumin-piperine to enhance permeability, both demonstrated positive outcomes with support from optimization analysis, FTIR, DSC, SEM, PXRD analysis, and dissolution studies.
Mycotools: An Automated and Scalable Platform for Comparative Genomics
Authors: Konkel Zachary , Slot Jason C.
Published: September 2023

Comparative genomics comprises analyses that investigate the genetic basis of organismal biology and ecology, which have also been applied to high throughput trait screening for applied purposes. The number of fungal genomes deposited in publicly available databases are currently in exponential growth. Due to the limited cutting-edge software availability and size or efficiency constraints of web-based analyses, comparative genomics research is often conducted on local computing environments. There is thus a need for an efficient standardized framework for locally assimilating, curating, and interfacing with genomic data. We present Mycotools as a comparative genomics database software suite that automatically curates, updates, and standardizes local comparative genomics. Mycotools incorporates novel analysis pipelines that are built on a suite of modules that streamline routine-to-complex comparative genomic tasks. The Mycotools software suite serves as a foundation for accessible and reproducible large-scale comparative genomics on local compute systems.
The Immune-Evasive Proline 283 Substitution in Influenza Nucleoprotein Increases Aggregation Propensity Without Altering the Native Structure
Authors: Yoon Jimin , Zhang Yu Meng , Her Cheenou , Grant Robert A. , Ponomarenko Anna M. , Ackermann Bryce E. , Debelouchina Galia T. , Shoulders Matthew D.
Published: September 2023

Nucleoprotein (NP) is a key structural protein of influenza ribonucleoprotein complexes and is central to viral RNA packing and trafficking. In human cells, the interferon induced Myxovirus resistance protein 1 (MxA) binds to NP and restricts influenza replication. This selection pressure has caused NP to evolve a few critical MxA-resistant mutations, particularly the highly conserved Pro283 substitution. Previous work showed that this essential Pro283 substitution impairs influenza growth, and the fitness defect becomes particularly prominent at febrile temperature (39 °C) when host chaperones are depleted. Here, we biophysically characterize Pro283 NP and Ser283 NP to test if the fitness defect is owing to Pro283 substitution introducing folding defects. We show that the Pro283 substitution changes the folding pathway of NP without altering the native structure, making NP more aggregation prone during folding. These findings suggest that influenza has evolved to hijack host chaperones to promote the folding of otherwise biophysically incompetent viral proteins that enable innate immune system escape.

Teaser

Pro283 substitution in flu nucleoprotein introduces folding defects, and makes influenza uniquely dependent on host chaperones.