bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of oculoplastic surgeons in minimally invasive cosmetic injectables
Authors: Meer Elana , Lopez Jacqueline , Lu Jonathan , Winn Bryan J. , Grob Seanna R.
Published: June 2024

Purpose of review

In recent years, the field of aesthetic medicine has witnessed a paradigm shift with an increasing demand for minimally invasive cosmetic procedures, including cosmetic injectables. This review aims to delineate the distinctive role played by oculoplastic surgeons in the administration of cosmetic injectables, comparing their expertise to that of nonphysician practitioners.

Recent findings

Complications arising from cosmetic injections are discussed, including skin discoloration, inflammation, necrosis, vision loss, retinal pathology, and central nervous system adverse effects. Injector expertise, patient factors, type of filler, location of injection, and management strategies are reviewed. Findings highlight diverse practitioner involvement, common adverse effects like skin necrosis and vision loss, with hyaluronic acid fillers being prominent. Areas at the highest risk for ocular complication include the glabella and nose with potential management involving dissolving fillers and reducing pressure. Emphasis is placed on expert injector selection and patient awareness.

The administration of cosmetic injectables requires a profound understanding of facial anatomy, vasculature, and potential complications. In contrast to nonphysician practitioners, oculoplastic and aesthetic surgeons bring a level of anatomical precision and clinical acumen that is essential for navigating the complexities of cosmetic injectables. Emphasis on training and collaboration among practitioners will be essential in advancing the field while prioritizing patient safety and satisfaction.
Glaucoma Severity Stage at First Visit at a University Eye Clinic in Congo
Authors: Elongo Gloria M. , Buvy Nicole N. , Kabedi Nelly N. , Mwanza Jean-Claude
Published: June 2024

Précis:

Initial presentation of glaucoma at a major eye clinic mostly features advanced disease with a high proportion of blindness. This is likely a microcosm of a nationwide issue requiring concerted strategies to detect glaucoma early.

Purpose:

To characterize the severity stage of new glaucoma patients in Congolese attending a university eye clinic.

Methods:

New glaucoma patients (n=118) were labeled as early or late presenters based on visual field sensitivity in the worse eye.

Results:

Mean age was 58.9±15.7 years, 51.7% were males. Overall, the worse eye had advanced, whereas the better eye had moderate glaucoma, with an asymmetry of −7.4 dB (P<0.001). Blindness was present in 30.5% of worse and 5.1% of better eyes. Seventy-two patients (61.0%) were late presenters. Visual acuity was lower (P<0.001), intraocular pressure (IOP) higher (P=0.02), cup-to-disc ratio larger (P=0.011), and retinal nerve fiber layer thinner (P=0.001) in late presenters’ worse than better eye. The worse and better eyes of late presenters had advanced glaucoma, with a −9.6 dB interocular asymmetry (P<0.001); 40.3% and 8.3% were blind, respectively. In early presenters, the worse and better eyes had moderate and early disease, respectively; the asymmetry was −3.2 dB (P<0.001), and 15.2% were blind. Overall, 58.5% and 65.3% presented with advanced disease in the worse eye based on visual field and cup-to-disc ratio criteria of the Canadian Ophthalmological Society staging scale, respectively.

Conclusions:

Most new glaucoma patients had bilateral advanced but asymmetric disease. These findings call for the establishment of community-based measures for early detection of glaucoma and a referral network system connecting community healthcare to tertiary eye clinics.
Autosomal Dominant Tubulointerstitial Kidney Disease–UMOD: A Monogenic Renal Disease that Cannot Be Ignored
Authors: Tian Xinyuan , Chen Yuqing
Published: June 2024

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of monogenic renal diseases characterized by autosomal dominant inheritance and progressive tubulointerstitial damage with bland urinary sediment. With the discovery of pathogenic variants, ADTKD was recognized as the most frequent non-polycystic genetic kidney disease. ADTKD–UMOD is caused by pathogenic variants of UMOD (coding gene of uromodulin) and is the most common subtype of ADTKD. With the improved awareness of the disease and the advance of genetic testing technology, cohort studies on affected families have gradually increased and deepened our understanding of the clinical and genetic spectrum of ADTKD–UMOD. In addition, extensive research has been conducted on the pathogenetic mechanism. This review highlights recent research progress in the genetic and clinical spectrum, as well as the underlying mechanisms of ADTKD–UMOD.
The effect of a pre-operative and post-operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (the PERIOP-OG trial): a randomized controlled trial
Authors: Loughney Lisa , Bolger Jarlath , Tully Roisin , Sorensen Jan , Bambrick Marie , Carroll Paul A. , Arumugasamy Mayilone , Murphy Thomas J. , McCaffrey Noel , Robb William B. ,   on Behalf of the PERIOP-OG Working Group
Published: June 2024

Introduction:

Although the benefits of post-operative rehabilitation in cancer surgery are well established, the role of prehabilitation is less defined. Oesophagogastric cancers present a unique opportunity to study the impact of prehabilitation during the neoadjuvant window, whether with chemotherapy or chemoradiotherapy (NCT) in patients who are frequently nutritionally depleted. This trial examines the impact of a community-based exercise programme on patient fitness during and after the neoadjuvant window.

Methods:

A pragmatic, randomized controlled multicentre trial was undertaken in three centres. Inclusion criteria were patients aged at least 18 years planned for NCT and esophagectomy or gastrectomy. Participants were randomized 1:1 to an exercise prehabilitation group (EX) or to usual care (UC). The primary endpoint was cardiorespiratory fitness between baseline and pre-surgery time point using the 6-minute walk test (MVT). Secondary endpoints included a hand dynamometer, 10-s sit-to-stand, activity behaviour, body mass index, semi-structured interviews, questionnaires assessing the quality of life, surgical fear, general self-efficacy and mastery.

Results:

Between March 2019 and December 2020, 71 participants were recruited: EX (n=36) or UC (n=35). From baseline to pre-surgery, the difference-in-difference (DID) for EX showed a significant improvement in 6MWT of 50.7 m (P=0.05) compared to UC [mean (SD): 522.1 m (+/−104.3) to 582.1 m (+/−108) vs. 497.5 m (+/−106.3) to 506.0 m (+/−140.4). There was no statistically significant DID for secondary outcome measures.

Conclusions:

This community exercise prehabilitation programme significantly improves physical fitness for surgery, is feasible and provides a standardized framework for the prescription of exercise in oesophagogastric cancer patients undergoing NCT.
Patients with stage IV colorectal carcinoma selected for palliative primary tumor resection and systemic therapy survive longer compared with systemic therapy alone: a retrospective comparative cohort study
Authors: Mantke Rene , Schneider Constanze , von Ruesten Anne , Hauptmann Michael
Published: June 2024

Objective:

To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only (SYST).

Background:

About 20–25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent.

Methods:

Mortality after PTR+SYST was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012–2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG greater than 2, unknown metastatic status or unclear grading.

Results:

Of 480 patients, 416 died during an average follow-up of 23 months in mean. Twelve-month survival was 75% after PTR+SYST compared with 49% after SYST [hazard ratio (HR)=0.39, 95% CI 0.29–0.53, P<0.001]. The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43–0.66, P<0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry.

Conclusion and relevance:

Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to the selection of patients or PTR remains unclear. At present, the current practice of selecting patients for PTR appears to do no harm.
Comparison of short-term outcomes of robotic versus open pancreaticoduodenectomy: a meta-analysis of randomized controlled trials and propensity-score-matched studies
Authors: Tang Gang , Zhang Linyu , Xia Lingying , Zhang Jie , Chen Rui , Zhou Rongxing
Published: June 2024

Background:

Robotic pancreaticoduodenectomy (RPD) is used more commonly, but this surge is mostly based on observational data. This meta-analysis aimed to compare the short-term outcomes between RPD and open pancreaticoduodenectomy (OPD) using data collected from randomized controlled trials (RCTs) and propensity-score-matched (PSM) studies.

Methods:

We searched PubMed, Cochrane Library, Embase, and Web of Science databases for RCTs and PSM studies comparing RPD and OPD. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated.

Results:

Twenty-four studies, encompassing two RCTs and 22 PSM studies, were included, with a total of 9393 patients (RPD group: 3919 patients; OPD group: 5474 patients). Although RPD was associated with a longer operative time (MD, 61.61 min), patients may benefit from reduced blood loss (MD, −154.05 ml), shorter length of stay (MD, −1.60 days), lower blood transfusion rate (RR, 0.85), and wound infection rate (RR, 0.61). There were no significant differences observed in 30-day readmission (RR, 0.99), 90-day mortality (RR, 0.97), overall morbidity (RR, 0.88), major complications (RR, 1.01), reoperation (RR, 1.08), bile leak (RR, 1.01), chylous leak (RR, 0.98), postoperative pancreatic fistula (RR, 0.97), post-pancreatectomy hemorrhage (RR, 1.15), delayed gastric emptying (RR, 0.88), number of harvested lymph nodes (MD, −0.12), and R0 resection (RR, 1.01) between the groups.

Conclusions:

Although some short-term outcomes were similar between RPD and OPD, RPD exhibited reduced intraoperative blood loss, shorter hospital stays, lower wound infection, and blood transfusion rates. In the future, RPD may become a safe and effective alternative to OPD.
Semaglutide outperforms insulin in restoring neutrophil function against implant-related infection in diabetic and obese mice: experimental research
Authors: Liu Tiexin , Zhou Lenian , Chen Yiwei , Lin Junqing , Zhu Hongyi
Published: June 2024

Background:

Bone and joint infections (BJI) are a significant complication after arthroplasty and fracture fixation, particularly challenging in patients with type 2 diabetes mellitus (T2DM) and obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has shown efficacy in managing T2DM and obesity. However, its impact on BJI risk and neutrophil function remains unclear. To investigate whether preoperative semaglutide treatment (1) reduces the risk of BJI in diabetic and obese mice undergoing intra-articular implants, and (2) outperforms insulin in restoring neutrophil function to mitigate implant-related infection.

Methods:

A C57BL/6 mouse model of T2DM/obesity was induced using a high-fat diet (HFD) for 12 weeks. Mice received preoperative insulin or semaglutide therapy for 1–28 days. BJI risk was assessed using an intra-articular-implant model challenged with Staphylococcus aureus or Escherichia coli. The neutrophil function was evaluated through bactericidal activity, superoxide production, and migration ability.

Results:

Semaglutide treatment led to a significant and sustained reduction in body weight and improved glucose tolerance in HFD mice. Both insulin and semaglutide therapies significantly reduced BJI risk, with semaglutide showing a more pronounced effect over time. Semaglutide therapy also enhanced neutrophil bactericidal activity, superoxide production, and migration ability compared to insulin therapy.

Conclusions:

Preoperative semaglutide treatment effectively reduces BJI risk and improves neutrophil function in diabetic and obese mouse models. These findings suggest that semaglutide may be a promising pharmacological intervention to mitigate infection risk in orthopedic patients with T2DM or obesity.
Nutritional aspects in patients with gastroparesis
Authors: Wierzbicka Adrianna , Ukleja Andrew
Published: June 2024

Purpose of review

The purpose of this review was to highlight most recent updates on nutritional aspects in gastroparesis (GP) focusing on dietary recommendations, utilization of enteral and parenteral nutrition, endoscopic and surgical interventions.

Recent findings

Recent data addressed eating patterns, nutritional interventions, and clarifications on the role of endoscopic and surgical interventions underlying an impact on nutritional management of GP patients. They support the importance of gastroparesis-specific diet in addition to drug therapy, and confirm the benefits of a modified low-fat, low-fiber diet. Current guidelines suggest a new approach to GP management based on predominant symptoms. Gastric peroral endoscopic pyloromyotomy (G-POEM) and surgical gastric electrical stimulator (GES) placement may be considered in individuals with nausea and vomiting before the need for jejunostomy tube placement for enteral feeding or parenteral nutrition.

Current literature supports the importance of dietary interventions, focusing on low-fat and low-fiber diets, in addition to drug therapies. Severely fiber-restrictive diets may not be necessary. There is enhanced understanding when jejunal feeding should be incorporated for refractory cases with consideration of G-POEM or/and GES even before jejunal tube placement. This approach will require patient evaluation in specialized motility centers.
Risk and factors determining diabetes after mild, nonnecrotizing acute pancreatitis
Authors: Pichardo-Lowden Ariana , Goodarzi Mark O. , Trikudanathan Guru , Serrano Jose , Dungan Kathleen M.
Published: June 2024

Purpose of review

Diabetes mellitus (DM) is relatively common following acute pancreatitis (AP), even after mild acute pancreatitis (MAP), the most frequent AP presentation, in which there is no overt beta cell injury. Post-AP related diabetes is widely misdiagnosed, resulting in potentially inappropriate treatment and worse outcomes than type 2 diabetes (T2D). Thus, it is important to understand risk across the spectrum of AP severity.

Recent findings

Biological mechanisms are unclear and may include local and systemic inflammation leading to beta cell dysfunction and insulin resistance, altered gut barrier and/or gut peptides and possibly islet autoimmunity, though no studies have specifically focused on MAP. While studies examining clinical risk factors on MAP exclusively are lacking, there are studies which include MAP. These studies vary in scientific rigor, approaches to rule out preexisting diabetes, variable AP severity, diagnostic testing methods, and duration of follow-up. Overall, disease related factors, including AP severity, as well as established T2D risk factors are reported to contribute to the risk for DM following AP.

Though numerous studies have explored risk factors for DM after AP, few studies specifically focused on MAP, highlighting a key knowledge gap that is relevant to the majority of patients with AP.
Labor Support during the Early Months of the COVID-19 Pandemic in the United States
Authors: Tucker Janet Adams , Waller Melody , Fouquier Kate , Fant Melanie , Rhoads Sarah
Published: June 2024

Purpose:

To describe the experiences of registered nurses and certified nurse midwives who provided labor support and care in the early months of the COVID-19 pandemic.

Study Design and Methods:

A descriptive, qualitative approach was used to explore nurses' and midwives' perceptions via in-depth interviews. Data were analyzed via thematic analysis.

Results:

Thirteen nurses, four of whom were also midwives, participated in semi-structured interviews. All provided care during the first 9 months of the pandemic and represented seven states across the United States. The analysis revealed an overarching theme, A New World but still a Celebration. This overarching theme encompasses participants' accounts of trying to provide the same support, presence, and celebration while dealing with constant policy changes, the impact of limited family presence in labor, and their own fears and risks. Four sub-themes were identified: The Impact of Nursing during COVID-19; Challenges, Changes, and Consequences; Unexpected Benefits; and The Cost.

Clinical Implications:

The first year of the COVID-19 pandemic saw unprecedented challenges for nurses. Practice changes due to these changing policies had negative and positive effects. Negative practices affected family support, decreased interprofessional collaboration, and caused shorter hospital stays for new mothers. Some positive aspects of practice changes included additional time for mother–newborn bonding due to restrictive visitation policies, increased initiation of breastfeeding, and focused patient education. Nurses across the United States are still coping with practice changes from the pandemic. Our study highlights the need to support nurses in adapting care in the midst of practice changes.
Pre-Pandemic Versus Early COVID-19 Perinatal Outcomes at a Military Hospital
Authors: Gibson Brandi L. , Urbieta Dehussa , Sweeney Sheila , Ferguson Jane A. , Glaser Dale , Marter Abigail Yablonsky
Published: June 2024

Purpose:

The purpose of this study was to examine the impact of the first year of COVID-19 pandemic on maternal and neonatal outcomes at a large military treatment facility in Southern California.

Study Design and Methods:

A retrospective review of maternal and neonatal medical records was conducted between January 1, 2019, and December 31, 2020. Outcomes measured included stillbirth rate, neonatal intensive care unit admission, neonatal death, cesarean birth, and postpartum hemorrhage.

Results:

A total of 4,425 records were analyzed. Rates of stillbirth between the years did not vary. The neonatal death rate decreased more than 50% in 2020 (p = .149). Cesarean births rose by 2.7% in 2020 (p = .046). Rates of postpartum hemorrhage did not vary between years.

Clinical Implications:

The impact of COVID-19 on maternal and neonatal outcomes at a military treatment facility in the first year of the COVID-19 pandemic provides guidance for optimizing perinatal health care. Vertical transmission of COVID-19 is low and routine testing of asymptomatic neonates of positive mothers may not be necessary. COVID-19 infections should not be an indication for cesarean birth and are not associated with neonatal deaths or NICU admission.
Fatigue Is Associated With Perceived Effort and 2-Dimensional Reach Performance After Stroke
Authors: Goh Hui-Ting , Stewart Jill , Becker Kevin
Published: June 2024

Background and Purpose:

Poststroke fatigue (PSF) is prevalent and often manifests as high perceived effort during activities. Little is known about how PSF influences goal-directed reaching after stroke. The purpose of this study was 2-fold (1) to evaluate how perceived effort changed when individuals with stroke performed a reaching task with various demands and (2) to determine whether PSF was associated with perceived effort during reaching and reach performance.

Methods:

Thirty-six individuals with chronic stroke performed 2-dimensional reach actions under varied conditions with the more and less affected arms. Perceived effort during reaching was assessed using rating of perceived exertion (RPE) and Paas Mental Effort Rating Scale (MERS). Derived reach kinematics were used to quantify reach performance. The Fatigue Severity Scale (FSS) was administered to assess fatigue severity.

Results:

Perceived effort was higher when participants reached with the more affected arm, reached toward far and small targets, and performed memory-guided reaching. Both RPE and MERS significantly correlated with the FSS score (r = 0.50 and 0.35, respectively, P < 0.05). Further, FSS correlated with movement time during the more affected arm reaching (ρ = 0.40, p < 0.05) and reach performance discrepancy between the fast and self-selected speed conditions when participants performed with the less affected arm (ρ = 0.36, P < 0.05). Exploratory analysis revealed that the relationship between fatigue and reach control appeared to be modulated by task demand.

Discussion and Conclusions:

PSF is associated with perceived effort during reaching and reach performance after stroke. These relationships might offer insights into arm performance in the real world after stroke.

Video Abstract:

for more insights from the authors Supplemental Digital Content available at http://links.lww.com/JNPT/A476
Robotic exoskeleton-assisted gait training in patients with motor incomplete myelopathy
Authors: Gupta Anupam , Prakash Navin B. , Honavar Preethi , S Jotheeswaran , Khanna Meeka , Ramakrishnan Subasree
Published: June 2024

Objectives:

To assess the effect of gait training with robotic exoskeleton-assisted rehabilitation systems on gait parameters, balance, and overall disability in motor incomplete myelopathy.

Design:

Prospective pre-post study.

Setting:

Neurological rehabilitation unit in a tertiary university teaching hospital.

Participants:

Thirty-four motor incomplete myelopathy patients [22 males, mean age 36.7 y (12.7)] were included in this prospective, pre-post study. Twenty-two had nontraumatic etiology, and 17 had tetraplegia. American Spinal Injury Association impairment scale suggested 23 as C and 11 as American Spinal Injury Association impairment scale-D. The mean duration of the lesion was 333 days.

Intervention:

Twenty-four sessions of robotic gait training (1-h session, 5–6 sessions/wk) for 4–6 weeks.

Outcome measures:

Gait speed was assessed using a 10-meter walk test (10MWT), endurance with a 2-minute walk test (2MWT) and 6-minute walk test (6MWT), walking ability by Walking Index in Spinal Cord Injury-walking index for spinal cord injury II, functionality using Spinal cord Independence Measure-SCIM III, and balance by Timed-up-and-go (TUG) test.

Results:

At baseline, 20 patients were nonwalkers-NWB, and 14 were walkers-WB. The walking index for spinal cord injury II and SCIM III suggested significant improvement in both groups by the end of the study (P<0.05). Among the WB group, 10MWT, 2MWT, and TUG showed significant improvement (P=0.004, 0.02, and 0.01, respectively) with training. Patients in NWB group were able to perform 10MWT, 2MWT, 6MWT, and TUG by the end of the study.

Conclusions:

Gait training with robotic exoskeleton-assisted rehabilitation systems can lead to a significant improvement in gait endurance, speed, balance, and functional outcomes in individuals with incomplete myelopathy. The effect is more pronounced among already ambulatory patients.
Breaking Down Silos in the Workplace: A Framework to Foster Collaboration
Authors: Jones Anita A. , Uhd Justin , Kabore Charlotte D. , Cornett Kelly A.
Published: June 2024

Introduction:

Employees are often placed within an organization based on their respective roles or duties, which can lead to vertical and horizontal organizational silos. Organizational silos may restrict information, resources, and stymie progress and innovation. This analysis presents a framework to mitigate silos and overcome communication barriers within an organization by increasing collaboration.

Methods:

The project team examined results from the Centers for Disease Control and Prevention (CDC), the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) 2020 Employee Viewpoint Survey Results and conducted 19 key informant discussions with NCCDPHP employees. Participants were asked to provide feedback on (1) understanding silos in the workplace and (2) best practices for reducing silos and fostering collaboration. A thematic analysis was conducted to understand organizational silos, the motivation to reduce silos, and identify best practices and strategies.

Results:

Respondents felt that siloing exists at the division and branch levels; however, 95% of respondents were motivated to reduce silos. Fifty-eight percent of respondents identified that institutional factors such as the organizational structure (n = 8) and red tape/bureaucracy (n = 3) contribute to siloing. Additional behaviors and actions that perpetuate silos were identified, and efforts to reduce silos were categorized to propose a model: Framework to Foster Collaboration for improving organizational collaborative efforts.

Discussion and Conclusion:

Key themes included inclusion, shared goals and vision, bi-directional communication, and relationship building and developing trust as critical elements for improving collaboration and creating synergy across teams in efforts to reduce silos in the workplace.
Interferon-free hepatitis C treatment increases a surrogate of atherosclerotic cardiovascular disease risk in Black veterans living with HIV
Authors: Mathur Poonam , Ramadhani Habib O. , Kaplan Roman , Stafford Kristen A. , Theppote Amanda , Wilson Eleanor
Published: June 2024

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.
Impact of efavirenz on hormone-positive breast cancer survival in women living with HIV
Authors: Johnson Arthur T. , Ntloedibe Taolo , Mendez Reyes Jose Euberto , Matshaba Mogomotsi S. , Dryden-Peterson Scott L. , Chiao Elizabeth Y.
Published: June 2024

Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz–estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0–72.2 and 51.1% (95% CI 34.0–76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.
Safety of tenofovir alafenamide in people with HIV who experienced proximal renal tubulopathy on tenofovir disoproxil
Authors: Campbell Lucy , Barbini Birgit , Cromarty Ben , Hamzah Lisa , Williams Deborah , Winston Alan , Post Frank A.
Published: June 2024

Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT.
Stereoelectroencephalography of the Deep Brain: Basal Ganglia and Thalami
Authors: Pati Sandipan , Agashe Shruti , Kheder Ammar , Riley Kristen , Gavvala Jay , McGovern Robert , Suresh Surya , Chaitanya Ganne , Thompson Stephen
Published: June 2024

Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy. This review explores the role of SEEG in elucidating the role of deep brain structures, namely the basal ganglia and thalamus, in epilepsy. SEEG advances understanding of their contribution to seizure generation, propagation, and control by permitting precise and minimally invasive sampling of these brain regions. The basal ganglia, comprising the subthalamic nucleus, globus pallidus, substantia nigra, and striatum, have gained recognition for their involvement in both focal and generalized epilepsy. Electrophysiological recordings reveal hyperexcitability and increased synchrony within these structures, reinforcing their role as critical nodes within the epileptic network. Furthermore, low-frequency and high-frequency stimulation of the basal ganglia have demonstrated potential in modulating epileptogenic networks. Concurrently, the thalamus, a key relay center, has garnered prominence in epilepsy research. Disrupted thalamocortical connectivity in focal epilepsy underscores its significance in seizure maintenance. The thalamic subnuclei, including the anterior nucleus, centromedian, and medial pulvinar, present promising neuromodulatory targets, suggesting pathways for personalized epilepsy therapies. The prospect of multithalamic SEEG and thalamic SEEG stimulation trials has the potential to revolutionize epilepsy management, offering tailored solutions for challenging cases. SEEG's ability to unveil the dynamics of deep brain structures in epilepsy promises enhanced and personalized epilepsy care in our new era of precision medicine. Until deep brain SEEG is accepted as a standard of care, a rigorous informed consent process remains paramount for patients for whom such an exploration is proposed.
Evaluation of an optimal agar medium for detecting hypervirulent Klebsiella pneumoniae using string test
Authors: Watanabe Naoki , Masuda Akari , Watari Tomohisa , Otsuka Yoshihito , Yamagata Kazufumi , Fujioka Miyuki
Published: June 2024

1. Abstract

The string test is a screening method for detecting hypervirulent Klebsiella pneumoniae (hvKp). Agar media are used for string tests; however, the effect of the type of media on the test results remains unclear. We aimed to determine the optimal agar medium and cutoff value for the string test. We performed the string test on 99 Klebsiella strains using different agar media: sheep blood, chocolate, Drigalski's, and MacConkey. Diagnostic accuracy was calculated in concordance with the rmpA, rmpA2, or iucA gene levels. The diagnostic accuracy rates for sheep blood, chocolate, Drigalski's, and MacConkey agar were 0.79, 0.75, 0.73, and 0.64, respectively. When the cutoff was changed from 5 to 10 mm, the diagnostic accuracy rate for sheep blood agar decreased from 0.79 to 0.65. Our findings suggest that the type of agar medium impacts string test results, and sheep blood agar with a 5 mm cutoff is the optimal condition for detecting hvKp.
Towards routine proteome profiling of FFPE tissue: Insights from a 1,200 case pan-cancer study
Authors: Tüshaus Johanna , Eckert Stephan , Fraefel Marius , Zhou Yuxiang , Pfeiffer Pauline , Halves Christiane , Fusco Federico , Weigl Johannes , Hönikl Lisa , Butenschön Vicki , Todorova Rumyana , Rauert-Wunderlich Hilka , The Matthew , Rosenwald Andreas , Heinemann Volker , Holch Julian , Meyer Bernhard , Weichert Wilko , Mogler Carolin , Hendrik-Kuhn Peer , Kuster Bernhard
Published: June 2024

Proteome profiling of formalin-fixed paraffin-embedded (FFPE) specimens has gained traction for the analysis of cancer tissue for the discovery of molecular biomarkers. However, reports so far focused on single cancer entities, comprised relatively few cases and did not assess the long-term performance of experimental workflows. Here, we did so by analyzing 1,220 tumors from six cancer entities processed over the course of three years. Key findings include the need for a new normalization method ensuring equal and reproducible sample loading for LC-MS/MS analysis across cohorts, showing that tumors can, on average, be profiled to a depth of >4,000 proteins and discovering that current software fails to process such large data sets. We report the first comprehensive pan-cancer proteome expression resource for FFPE material comprising 11,000 proteins which is of immediate utility to the scientific community by way of a web resource. It enables a range of analysis including quantitative comparisons of proteins between patients or cohorts or the discovery of protein fingerprints representing the tissue of origin, or proteins enriched in certain cancer entities.
DirectHRD enables sensitive scar-based classification of homologous recombination deficiency (HRD)
Authors: Liu Ruolin , Roberts Eugenia , Parsons Heather A. , Stover Elizabeth H. , Choudhury Atish D. , Rhoades Justin , Blewett Timothy , Yang David D. , Liu Joyce F. , Mayer Erica L. , Adalsteinsson Viktor A.
Published: June 2024

Homologous recombination deficiency (HRD) is a predictive biomarker for efficacy of PARP inhibition and platinum chemotherapy but remains challenging to detect from low tumor fraction samples such as liquid biopsies. Here, we describe DirectHRD, a whole-genome sequencing (WGS) scar-based classifier that is 10x more sensitive than state-of-the-art methods. DirectHRD can detect HRD at >=1% tumor fraction using 50x WGS of cell-free DNA.
Phylogenetics and genomic variation of two genetically distinctHepatocystisclades isolated from shotgun sequencing of wild primate hosts
Authors: Haffener Paige E. , Hopson Helena D. , Leffler Ellen M.
Published: June 2024

Hepatocystisare apicomplexan parasites nested within thePlasmodiumgenus that infect primates and other vertebrates, yet few isolates have been genetically characterized. Using taxonomic classification and mapping characteristics, we searched forHepatocystisinfections within publicly available, blood-derived low coverage whole genome sequence (lcWGS) data from 326 wild non-human primates (NHPs) in 17 genera. We identified 30Hepatocystisinfections inChlorocebusandPapiosamples collected from locations in west, east, and south Africa.Hepatocystis cytbsequences fromPapiohosts phylogenetically clustered with previously reported isolates from multiple NHP taxa whereas sequences fromChlorocebushosts form a separate cluster, suggesting they represent a new host-specific clade ofHepatocystis.Additionally, there was no geographic clustering ofHepatocystisisolates suggesting both clades ofHepatocystiscould be found in NHPs throughout sub-Saharan Africa. Across the genome, windows of high SNP density revealed candidate hypervariable loci includingHepatocystis-specific gene families possibly involved in immune evasion and genes that may be involved in adaptation to their insect vector and hepatocyte invasion. Overall, this work demonstrates how lcWGS data from wild NHPs can be leveraged to study the evolution of apicomplexan parasites and potentially test for association between host genetic variation and parasite infection.

Author Summary

Non-human primates are hosts to many species ofPlasmodium, the parasites that cause malaria, and a closely related group of parasites calledHepatocystis. However, due to restrictions and challenges of sampling from wild populations, we lack a complete understanding of the breadth of diversity and distribution of these parasites. Here, we provide a framework for testing already-sampled populations for parasite infections using whole genome sequences derived from whole blood samples from the host. Following taxonomic classification of these sequences using a database of reference genomes, we mapped reads to candidate parasite genomes and used an unsupervised clustering algorithm including coverage metrics to further validate infection inferences. Through this approach, we identified 30Hepatocystisinfections from two genetically distinct clades ofHepatocystisin African non-human primates and described genes that may be under immune selection in each. Most importantly, the framework here can be applied to additional sequencing datasets from non-human primates and other vertebrate hosts as well as datasets from invertebrate vectors. Therefore, this approach could greatly improve our understanding of where these parasites are found, their host-specificity, and their evolutionary history. This framework may also be adapted to study evolution in other host-pathogen groups.
De novo whole-genome assembly and annotation of a high-quality coffee variety from the primary origin of coffee,Coffea arabicavar. Geisha
Authors: Medrano Juan F. , Cantu Dario , Minio Andrea , Dreischer Christian , Gibbons Theodore , Chin Jason , Chen Shiyu , Van Deynze Allen , Hulse-Kemp Amanda M
Published: June 2024

Geisha coffee is recognized for its unique aromas and flavors and accordingly, has achieved the highest prices in the specialty coffee markets. We report the development of a chromosome-level, well-annotated, genome assembly ofCoffea arabicavar. Geisha, considered an Ethiopian landrace thatrepresents germplasm from the Ethiopian center of origin of coffee. We used a hybridde novoassembly approach combining two long-reads single molecule sequencing technologies, Oxford Nanopore and Pacific Biosciences, together with scaffolding with Hi-C libraries. The final assembly is 1.03GB in size with BUSCO assessment of the assembly completeness of 97.7% of single-copy orthologs clusters. RNAseq and IsoSeq data were used as transcriptional experimental evidence for annotation and gene prediction revealing the presence of 47,062 gene loci encompassing 53,273 protein-coding transcripts. Comparison of the assembly to the progenitor subgenomes, separated the set of chromosome sequences inherited fromC. canephorafrom those ofC. eugenioides., Corresponding orthologs between Geisha and Red Bourbon had a 99.67% median identity, higher than what we observe with the progenitor assemblies (median 97.28%). Both, Geisha and Red Bourbon contain an inversion on Chromosome 10 relative to the pseudomolecules of the genetic material inherited from the two progenitors that must have happened before the separation in the geographical migration of the two varieties. Lending support of a single allopolyploidization event that gave origin toC. arabicaafter the hybridization event with the two progenitor lines. Broadening the availability of high-quality genome assemblies ofCoffea arabicavarieties, paves the way for understanding the evolution and domestication of coffee, as well as the genetic basis and environmental interactions of why a variety like Geisha is capable of producing beans with such exceptional and unique high-quality.
Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury
Authors: Takatani Hirohide , Fujita Naoki , Imai Fumiyasu , Yoshida Yutaka
Published: June 2024

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion ofRhoAandPtenin corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI. Here, we examined the effects ofRhoA;Ptendeletion coupled with neural stimulation after cervical SCI. This combinatorial approach promoted more boutons on injured corticospinal neurons in the spinal cord compared to soleRhoA;Ptendeletion. AlthoughRhoA;Ptendeletion does not promote motor recovery in the forelimb after SCI, stimulating corticospinal neurons in those mice results in partial motor recovery. These results demonstrate that a combinatorial approach that pairs genetic modifications with neuronal stimulation can promote axon sprouting and motor recovery following SCI.
Bacterial population-level trade-offs between drought tolerance and resource acquisition traits impact decomposition
Authors: Malik Ashish A , Martiny Jennifer BH , Ribeiro Antonio , Sheridan Paul O , Weihe Claudia , Brodie Eoin L , Allison Steven D
Published: June 2024

Microbes drive fundamental ecosystem processes such as decomposition. Environmental stressors are known to affect microbes, their fitness, and the ecosystem functions that they perform, yet understanding the causal mechanisms behind this influence has been difficult. We used leaf litter on soil surface as a model in situ system to assess changes in bacterial genomic traits and decomposition rates over 18 months with drought as a stressor. We hypothesized that genome-scale trade-offs due to investment in stress tolerance traits under drought reduce the capacity for bacterial populations to carry out decomposition; and that these population-level trade-offs scale up to impact emergent community traits thereby reducing decomposition rates. We observed drought tolerance mechanisms that were heightened in bacterial populations under drought, identified as higher gene copy numbers in metagenome-assembled genomes. A subset of populations under drought had reduced carbohydrate-active enzyme genes which suggested - as a trade-off - a decline in decomposition capabilities. These trade-offs were taxonomically structured as distinct patterns appeared in populations across families. We show that trait-tradeoffs in bacterial populations under drought could scale up to reduce overall decomposition capabilities and litter decay rates. Using a trait-based approach to assess the population ecology of soil bacteria, we demonstrate genome-level trade-offs in response to drought with consequences for decomposition rates.
The importance of mistakes: Variation in spores reveals trade-offs for range expansion in the xeric-adapted Australasian speciesCheilanthes distans(Pteridaceae)
Authors: Sosa Karla
Published: June 2024

Biological trade-offs present a central issue for evolutionary biology: it has been a fundamental understanding within the field that limits exist on the phenotypic traits a species is able to exhibit in part due to trade-offs. Reproduction—with its myriad forms—has been studied extensively in the context of these dynamics. And while considerable literature has explored trade-offs between seed size and number and their associated environmental conditions, none has looked at spore size trade-offs in ferns. We can hypothesise potential trade-offs in spore size: smaller spores should be able to disperse farther, but may not have sufficient provisions to survive in environments that require them to remain at the gametophyte stage for longer periods if their germination cues are mismatched. Reproductive mode (sexual vs. asexual) and ploidy may also be playing a role. In order to study trade-offs related to spore size, I focus on the Australasian fern speciesCheilanthes distans(Pteridaceae), which is most often found in xeric environments, growing in crevices or on top of rocks which are haphazardly scattered across their range. Apomictic diplospores in this species are formed through first division restitution, a meiotic pathway particularly prone to mistakes in chromosome pairing and cell division (as compared to premeiotic endomitosis). Rather than being problematic, these mistakes ultimately lead to considerable additional variation in spore size, spore products (through a range of aneuploid spores), and spore ploidy. In this study, I explore trade-offs between spore size, dispersal, and germination, taking into account effects from reproductive mode and ploidy. I carried out an extensive survey ofC. distansspecimens to establish the prevalence of sexual vs. apomictic (asexual) specimens, and to describe in greater depth the variation in ploidy across the species. I also collected data on spore size and sporogenesis forms. With these data I then asked: is spore size correlated with range area or with germination? And does spore form correlate with either spore size or germination? Ultimately, I find that variations in sporogenesis may be leading to large variation in spore sizes—especially since spores traditionally considered abortive are in fact viable—and that this variation may provide abundant fodder for evolution to act through trade-offs between dispersal into large ranges and germination leading to establishment. Especially in light of the fact that many spores that were historically considered abortive are fully viable and likely shaping evolution in important ways, it is worth remarking on what these results illustrate more broadly: the way in which we have constructed ‘disability’ ultimately affects how we perceive so-called ‘genetic errors’—both in humans and in other species—and thus limits what we allow ourselves to imagine ‘disabled’ beings are capable of.
Short steps can take you far: Phylogenetic analysis of AustralasianCheilanthes distansreveals frequent shorter-range dispersal
Authors: Sosa Karla
Published: June 2024

Biologists have long pondered species’ geographical distributions and sought to understand what factors drive dispersal and determine species ranges. In considering plant species with large ranges, a question that has remained underexplored is whether large ranges are attained primarily through many instances of short scale dispersal or whether instead widespread ranges are attained by propagules with increased dispersal distances. Ferns provide an ideal system to explore this question as their propagules are very small spores, which have been theorised can be carried by wind to essentially anywhere on the planet. Unfortunately, population-level genetic data in ferns is relatively uncommon, limiting our ability to answer this and related questions. For this work, I focus onCheilanthes distans(Pteridaceae) as a study system, a widespread fern with extensive spore variation that occurs over Australia and into New Zealand/Aotearoa, New Caledonia, and other Pacific islands. I sampled widely across the species’ range, in addition to across AustralasianCheilanthes(as a robust tree for the genus does not exist), ultimately building a phylogeny based on the GoFlag 451 bait set. With these data, we can investigate additional questions, including whether reproductive mode, polyploidy, or lineage influence dispersal, as well as whether movement is occurring randomly or is instead asymmetrical. I explored the relationships between sexual and apomictic specimens to understand whether the former are the parental lineages to apomictic plants and whether we find evidence for apomictic plants dispersing out of a small parental range. I investigated how many times polyploid lineages have arisen inC. distansand whether they are each limited geographically, perhaps forming isolated ranges that collectively result inC. distans’larger range. Additionally, I generated estimates for ancestral ranges and dispersal between populations to understand whether certain lineages are limited to particular geographic regions, to explore the directionality of dispersal, and to assess whether most movement is happening over short or long distances. Particularly interestingly, I find that most dispersal in this species appears to occur over smaller steps rather than longer jumps, underscoring how short movement can nevertheless allow for establishment of large ranges; this dispersal is not limited phylogenetically and seems to occur equally for all lineages. What is more, I find evidence for asymmetrical dispersal directionality, apparently most frequently tracking trade winds. These findings demonstrate the importance of population-level data, and provide concrete results that add nuance to long-standing dispersibility hypotheses in the fern community that have, until now, lacked empirical data.