bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Atrial Shunt Therapy for Heart Failure: A Comprehensive Review of the Atrial Coronary Sinus Shunt
Authors: Patel Manav , Tated Ritu Chandra Prakash , Maheta Darshil Kumar , Agrawal Siddharth Pravin , Frishman William H. , Aronow Wilbert S.
Published: August 2024

Heart failure is a prevalent and severe medical condition characterized by the heart’s inability to pump blood efficiently, leading to poor circulation and symptoms such as pulmonary congestion. Despite advancements in medical treatments, many patients continue to experience significant symptoms with reduced quality of life. This article explores the left atrial coronary sinus shunt as an innovative interventional strategy to address hemodynamic issues in heart failure. The shunt aims to decrease left atrial pressure and alleviate pulmonary congestion by creating a connection between the left atrium and the coronary sinus.
Complex Frontal Bone Reconstruction Using Computer-designed Polyetheretherketone Implant: Case Report and Literature Review
Authors: Liu Yueqi , Xie Shao , Ding Jiahai , Zhang Yushun , Deng Liyi , Yao Yuancheng , Xiong Yang , Chen Yuliang , Wang Lei , Liu Yong
Published: August 2024

Calvarial reconstruction of complex frontal bone defects after head trauma surgery is challenging, especially when it coexists with an absence of eyebrow arch and supraorbital wall. Due to various reasons, the patient’s bone flap could not be used. Common alternative materials include polyetheretherketone (PEEK) and titanium. Careful and detailed planning is required to maximize functional and aesthetic reconstruction, thereby benefiting the patient. We present a case of a 36-year-old man who had multiple frontal bone defects after multiple operations for craniofacial fractures performed with reconstruction surgery using a PEEK implant successfully. With a follow-up for 2 years, the patient was satisfied with the long-term aesthetic effect without any consequences such as surrounding tissue infection or implant displacement. The authors believe that the PEEK implant has great potential for calvarial reconstruction due to its incredible strength, durability, and inertness.
Vascularized Omentum Lymphatic Transplantation as a Treatment for Chronic Inguinal Ulceration and Lymphedema
Authors: Tian Chenyang , Gao Xiaowen , Wang Kejia , Ji Peng , Zheng Zhao , Wang Yunchuan , Hu Dahai
Published: August 2024

Background:

After tumor resection, lymphadenectomy, and radiotherapy, recurrent lymphatic fluid leakage and infection can occur in the inguinal region, contributing to severe localized tissue fibrosis. When wounds form in this region, they tend to heal slowly over extended periods, and no optimal approach for treating these complex wounds has yet been established.

Methods:

Groin wound debridement and dissection of the vessels in the wound recipient site were performed by the burn surgeon. A general surgeon performed the laparoscopic partial omentum excision. One portion of the omentum was used to fill the large inguinal space, whereas the other portion was laid flat on the wound sites in the groin and anterior perineum to facilitate the restoration of appropriate lymphatic fluid reflux. The vessels of the omentum were microsurgically anastomosed with the vessels in the recipient site. Thin split-thickness slices of skin were then taken from this donor site based on the size of the wound.

Results:

After the successful establishment of revascularization between the flap and recipient sites, lymphatic fluid leakage was not observed in this patient. No inguinal wounding or lymphatic exudate were evident in the patient during follow-up, and significant improvements in lymphedema of the lower extremities were evident.

Conclusions:

In this article, we discuss the advantages and disadvantages of vascularized omentum lymphatic transplantation. Overall, this procedure represents a promising new approach for the treatment of refractory wounds caused by lymphatic fistulas.
Documented Initial Growth Does Not Necessarily Indicate Treatment for Sporadic Vestibular Schwannomas
Authors: Bourque Jean-Michel , Panizza Benedict J.
Published: August 2024

Objective

To report the natural history of vestibular schwannoma (VS) who elected an initial period of observation and identify prognostic factors. To describe the natural history of growing VS, identify prognostic factors, and review the most recent literature.

Study Design

Prospective cohort study and literature review.

Setting

Tertiary referral center.

Patients

Adult patients diagnosed with a VS between January 1998 and February 2023.

Intervention

Magnetic resonance imaging surveillance.

Main Outcome Measure(s)

Growth-free survival and subsequent growth-free survival considering significant growth as a change in size of ≥2 mm.

Results

Of 430 patients undergoing observation with serial magnetic resonance imaging, 193 (44.9%) demonstrated significant growth at a median of 1.6 years (interquartile range, 0.94–3.51). Of the 193 patients who presented an initial episode of growth, 137 elected to continue to be observed. Of those, 83 (60.6%) presented a second episode of growth at a median of 1.43 years (interquartile range, 1.00–2.49). The subsequent growth-free survival rates (95% confidence interval) at 1, 3, 5, 7, and 10 years were 91.79% (87.26–96.56%), 64.44% (56.56–73.42%), 52.52% (44.23–62.35%), 42.23% (33.92–52.56%), and 36.11% (27.89–46.76%), respectively. Univariate and multivariate Cox regression analyses showed that EC tumor location and initial growth rate were significant predictors of subsequent growth.

Conclusions

Close observation after documentation of growth is an appropriate management in well-selected cases given that only around 56% of the tumor will continue to grow. Extracanalicular tumor location and initial growth rate are promising prognostic factors to help determine which patient would be a better candidate for close surveillance after initial documentation of growth.
External Auditory Canal Erosion at the 6 O’clock Spot
Authors: Boya Mounika Naidu , Blumenstein Nicole , Redleaf Miriam
Published: August 2024

Objective

To report a common site of external ear canal erosion in multiple pathologies, located inferiorly at 6 o’clock.

Patients

Otology patients who came in 2023 for treatment of external auditory canal erosions.

Intervention

This clinical capsule is an observational report of the external canal’s propensity to erosion at the 6 o’clock location. Patient treatments were canalplasty, mastoidectomy, and medical management.

Main Outcome Measure

Documentation of the propensity to erosion at the 6 o’clock location in the external auditory canal. Locations of the niduses of prior series of external auditory canal pathologies are documented.

Results

Eight patients are presented with external auditory canal erosion in 10 ears originating at the 6 o’clock position medial to the bony-cartilaginous junction. No other patient with spontaneous canal erosion presented with their nidus of pathology in another canal location. (A review of 42 case series of 291 patients found that keratosis obturans and bisphosphonate-induced osteonecrosis tended to arise from the same 6 o’clock lateral bony canal location, while 26% of necrotizing otitis externa cases arose there.)

Conclusions

The “6 o’clock spot” in the external canal is a common location of canal erosion for spontaneous wax and keratin collections and may be the precursor to keratosis obturans, bisphosphonate-induced osteonecrosis of the ear canal, and necrotizing otitis externa.
Strategies for management of patients with elevated lipoprotein(a)
Authors: Ellberg Charlotte C. , Bhatia Harpreet S.
Published: August 2024

Purpose of review

There is growing literature that supports the testing of Lp(a). However, few patients are tested, including those with a personal or family history of cardiovascular disease (CVD). One often noted barrier to more widespread testing is uncertainty regarding what to do with an elevated Lp(a) level. Although guidelines vary, there is agreement on the use of Lp(a) as a risk enhancer to guide medical care and shared decision-making. This review will discuss a clinical approach with supporting evidence for management of patients with elevated Lp(a).

Recent findings

At the minimum, elevated Lp(a) increases cardiovascular risk and can be incorporated into existing risk stratification paradigms. The cornerstone of management is aggressive management of traditional cardiovascular risk factors, including LDL-cholesterol (LDL-C). More recent studies have highlighted the potential role for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), aspirin in primary prevention, and prolonged dual antiplatelet therapy in secondary prevention.

Although there is optimism for Lp(a)-targeted therapies in the near future, an elevated Lp(a) level is actionable today, and uncertainty regarding the management of patients with elevated Lp(a) should not be a barrier to more widespread testing.
Risk of dementia associated with the use of anticholinergic medications: a review of recent literature
Authors: Ziadeh Hachem , Rhodes Stephen , Sheyn David , Hijaz Adonis
Published: August 2024

Purpose of review

While there is an established association between the use of anticholinergic medications and its effects on cognition, the extent of this impact remains unclear. We outline recent studies addressing this topic.

Recent findings

We describe a series of recent articles discussing the risk of dementia associated with anticholinergic medication use in general, with further focus on the risk of overactive bladder (OAB) anticholinergic use, detailing short & long-term use effects, risk variation based on age and gender, and reporting alternative treatment options.

Anticholinergic medication use bears an increased risk of dementia development, and accelerated cognitive decline in individuals with preexisting dementia, with the risk being related to the medications dosages, length of exposure, and pharmacological profile. β3-adrenoceptor agonists have proven to be a potent alternative for OAB anticholinergics, owing to its safe profile in regards of no clear effects on cognitive function, and having similar efficacy in OAB treatment.
Severe Maternal Morbidity by Disability Status and Type in the United States
Authors: Akobirshoev Ilhom , Vetter Michael , Horner-Johnson Willi , Lomerson Nicole , Moore Simas Tiffany A. , Mitra Monika
Published: August 2024

OBJECTIVE:

To estimate the risk of severe maternal morbidity (SMM) among women with disabilities compared with those without disabilities in a nationally representative sample of U.S. delivery hospitalizations.

METHODS:

We conducted a retrospective cohort analysis using the 2016–2021 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. We identified delivery hospitalizations and disability status using International Classification of Diseases, Tenth Revision diagnosis codes. The primary outcome was SMM, which was determined using 21 indicators specified by the Centers for Disease Control and Prevention. We used Poisson regression to estimate unadjusted and adjusted relative risks (aRRs) and 95% CIs for the association between disability status and type with SMM outcomes.

RESULTS:

Among 4,331,457 delivery hospitalizations, 128,413 (3.0%) were to women with disabilities. Women with disabilities had significantly higher rates of SMM compared with those without disabilities (396/10,000 deliveries vs 177/10,000 deliveries). In fully adjusted models, women with disabilities had an aRR of 1.86 (95% CI, 1.80–1.91) for one or more SMM indicators. The risk of SMM varied by disability type, with the highest risks observed for women who had vision disabilities (aRR 3.02, 95% CI, 2.70–3.38) or had physical disabilities (aRR 2.44, 95% CI, 2.34–2.55). Women with disabilities had the highest risk for other medical complications (puerperal cerebrovascular disorders and sickle cell disease with crisis), followed by other obstetric complications, respiratory complications, cardiovascular complications, acute renal failure, sepsis, and bleeding complications compared with women without disabilities.

CONCLUSION:

Women with disabilities have a significantly higher risk of SMM during delivery compared with those without disabilities, with the magnitude of risk varying by disability type. Efforts to reduce SMM and maternal mortality in the United States must prioritize the unique needs of this population and ensure equitable, disability-competent care for all women.
Restriction of Surgical Options for Pelvic Floor Disorders
Authors: Lowder J. L. , Jeppson P. , Grimes C. L. , Asfaw T , Winkelman W. , Chang O. , Smilen S. W. ,   AUGS Publications Committee
Published: August 2024

(Abstracted from Urogynecology 2024;30:467–475

In 2013, the American Urogynecologic Society (AUGS) Board of Directors distributed a “Position Statement on Restriction of Surgical Options for Pelvic Floor Disorders” in response to limitations instituted by the US Food and Drug Administration (FDA) on the use of transvaginal mesh (TVM) for pelvic organ prolapse (POP) due to concerns about safety and effectiveness. This article is an update to that statement informed by additional clinical data, decisions from the FDA, and relevant guidelines regarding surgical mesh.
Does Recurrent Implantation Failure Exist? Prevalence and Outcomes of Five Consecutive Euploid Blastocyst Transfers in 123 987 Patients
Authors: Gill Pavan , Ata Baris , Arnanz Ana , Cimadomo Danilo , Vaiarelli Alberto , Fatemi Human M. , Ubaldi Filippo Maria , Garcia-Velasco Juan A. , Seli Emre
Published: August 2024

(Abstracted from Hum Reprod 2024;39(5):974–980

Recurrent implant failure (RIF) has been defined as repeated failed implantations following multiple embryo transfers. A landmark paper on RIF reported the cumulative sustained implantation and live birth rates achieved with 3 consecutive single euploid blastocyst transfers and found a similar live birth rate across the first 3 consecutive transfers with a “true” unexplained RIF rate of <5% in the in vitro fertilization population.
Electronic Nicotine-Delivery Systems for Smoking Cessation
Authors: Auer Reto , Schoeni Anna , Humair Jean Paul , Jacot-Sadowski Isabelle , Berlin Ivan , Stuber Mirah J. , Haller Moa Lina , Tango Rodrigo Casagrande , Frei Anja , Strassmann Alexandra , Bruggmann Philip , Baty Florent , Brutsche Martin , Tal Kali , Baggio Stéphanie , Jakob Julian , Sambiagio Nicolas , Hopf Nancy B. , Feller Martin , Rodondi Nicolas , Berthet Aurélie
Published: August 2024

(Abstracted from N Engl J Med 2024;390:601–610

In a recent systematic review of randomized controlled trials (RCTs), e-cigarettes were found to be more effective for tobacco smoking cessation than nicotine replacement therapy (NRT). Yet, limited evidence exists on the safety and efficacy of e-cigarettes over standard-of-care cessation counseling and their ability to relieve respiratory symptoms like cough and phlegm compared with quitting tobacco cigarettes.
Utility of SATB2 and MOC-31 Immunostains to Distinguish Between Poorly Differentiated Rectal Adenocarcinoma and Anal Squamous Cell Carcinoma
Authors: Fang Jiayun M. , Assarzadegan Naziheh , Cheng Jerome , Lamps Laura
Published: August 2024

Objectives:

Colorectal adenocarcinoma and squamous cell carcinoma (SCC) can arise in the anorectum and present a significant diagnostic challenge when poorly differentiated. Accurate diagnosis can significantly influence management, as the treatments for these conditions involve distinct neoadjuvant chemoradiotherapy regimens. MOC-31 and SATB2 have been utilized as specific markers of glandular differentiation and colorectal origin, respectively, but studies have shown that they may be positive in squamous cell carcinoma of other sites. This raises the concern that MOC-31 and SATB2 may be positive in squamous cell carcinoma of the anorectum, and overreliance on these stains may be a potential diagnostic pitfall in differentiating rectal poorly differentiated adenocarcinoma (PDA) from anal nonkeratinizing SCC.

Methods:

We identified biopsies from 10 rectal PDA and 17 anorectal nonkeratinizing SCC cases and stained them for MOC-31 and SATB2.

Results:

We found that MOC-31 was highly sensitive, being positive in 10/10 cases of rectal PDA, but not specific, as it was also positive in 11/17 SCC cases. In contrast, SATB2 was both sensitive, with positive staining in 10/10 rectal PDA cases, and specific, with negative staining in 17/17 SCC cases. This includes equivocal staining in 4 of these negative SCC cases. MOC-31 had a sensitivity of 100% and specificity of 35.3%, while SATB2 had a sensitivity of 100% and specificity of 100%.

Conclusions:

Unlike squamous mucosa of the head and neck, and esophagus, SCC of the anus does not frequently stain positively for SATB2. These data suggest that SATB2 is a reliable marker in distinguishing rectal PDA from anorectal nonkeratinizing SCC, whereas MOC-31 is commonly positive in SCC of the anus. It is also important to note that equivocal SATB2 staining may be seen in SCC.
Information Overload—Do We Read All the Posters Displayed Across the Walls on Hospital Wards?
Authors: Sahota Amunpreet , Wijayasiri Pramudi , Than Htet , Munir Mohsin , Sahota Opinder
Published: August 2024

Background and Objectives:

To establish whether posters displayed across the walls on hospital wards are read, what information is important, and how the information should be received.

Methods:

Sixty-eight staff and 32 patients’ relatives were interviewed across 3 older people’s medical wards followed by 20 follow-up secondary questionnaires postintervention.

Results:

Only 23% of those interviewed were able to recall any of the posters displayed, and of those, 34% did not find the information useful. Those interviewed were enthusiastic about utilizing alternative media. A quarter felt the walls across the hospitals wards should be for artwork. Among patients’ relatives interviewed, common information requests were “the discharge pathway,” “delirium,” and “falls.” Based on the initial findings, a targeted information board was installed and a mural was painted across the wall in one of the wards. Further post-intervention interviews with patients’ relatives showed that the board was well received, but further unmet information needs were uncovered. Despite the new mural, 45% called for more paintings.

Conclusion:

Most people ignore the posters displayed across the walls of hospital wards, and unmet information needs are rife. An appetite exists for alternative media. Paintings were earnestly called for, highlighting how a comforting environment could be part of the holistic care we offer patients in hospital.
Quantitative Evaluation of Noncontrast Magnetic Resonance Enterography for Active Inflammation in Crohn Disease Using Native T1 and T2 Mapping
Authors: Morimoto-Ishikawa Daisuke , Hyodo Tomoko , Komeda Yoriaki , Fukushima Hiroyuki , Itoh Makoto , Ueda Yu , Kudo Masatoshi , Saito Shigeyoshi , Ishii Kazunari
Published: August 2024

Purpose

The aim of this study was to investigate the utility of native T1 and T2 mapping in the bowel to evaluate disease activity in Crohn disease (CD) using endoscopy as the reference standard.

Methods

This was a prospective study. Magnetic resonance imaging was performed by using a 1.5-T Philips scanner. We used a modified look-locker inversion recovery and a multiecho gradient-spin-echo sequences for single breath-hold native T1 and T2 maps, respectively, for the short-axis image of the intestine, and the measurement at the most severe site was compared with partial Simple Endoscopic Score for Crohn's Disease (pSES-CD, assessed by an expert endoscopist). A pSES-CD ≥ 4 indicated active disease. Statistical analyses were performed using the Student t test, Spearman correlation, and receiver operating characteristic curve analysis.

Results

A total of 27 patients (mean age ± standard deviation, 37 ± 18 years; 20 men, 7 women) were included in this study. The native T1 value of active disease was significantly higher than that of inactive disease (1170.8 ± 100.5 milliseconds vs 924.5 ± 95.3 milliseconds; P = 0.018), but the T2 value was not significantly different between active and inactive disease (76.1 ± 7.8 milliseconds vs 69.3 ± 10.9 milliseconds; P = 0.424). A good correlation was found between native T1 value and pSES-CD (ρ = 0.71; P < 0.001) but not between T2 value and pSES-CD (ρ = 0.06; P = 0.790). The area under the receiver operating characteristic curve for differentiating the disease activity was 0.96 (95% confidence interval [CI]: 0.90–1.00) for T1 values and 0.68 (95% confidence interval: 0.41–0.96) for T2 values.

Conclusions

Native T1 mapping could be potentially used as a noninvasive method to differentiate disease activity in patients with CD and may be superior to T2 mapping for this purpose.
Application of Submucosal Trans-Septal Suturing Technique in a Septal Extension Graft With Porous High-Density Polyethylene and Concurrent Nasal Lateral Osteotomy
Authors: Gu Tianya , Gan Yufeng , Huang Xin , Peng Su , Wu Jie , Chen Xiang , Guo Zongke , Lin Jinde
Published: August 2024

Background:

Recently, a submucosal trans-septal suturing (STSS) technique was introduced to obviate the dead space of septum after septal extension graft (SEG) with porous high-density polyethylene (pHDPE).

Objective:

To investigate STSS technique after SEG with pHDPE and concurrent nasal lateral osteotomy (LO).

Methods:

A retrospective study was conducted in 53 patients who underwent a STSS technique after SEG with pHDPE and concurrent LO. The postoperative discomfort (nasal pain and obstruction), the width of the nasal bony base, Nasal Obstruction Symptom Evaluation (NOSE), Rhinoplasty Outcomes Evaluation (ROE), and complications were recorded and assessed.

Results:

The mean surgical duration of STSS was 862.53±227.73 seconds. The maximal mean score of postoperative nasal pain and nasal obstruction was 2.132±0.921 and 1.868±0.8995, respectively. The values on the width of the nasal bony base and ROE were significantly improved after surgery. There was no significant difference in NOSE values preoperatively versus 6 months postoperatively. An infection was found in 1 patient, a recurrent minor bleeding of septum in another patient, and a symptomatic nasal obstruction in other 2 patients. There was no major bleeding, hematoma, foreign body sensation, septal perforation, and other infection.

Conclusion:

STSS can eliminate the postoperative dead space of nasal septum with low discomfort and complications, and help to avoid a lateral displacement of osteotomized nasal bony segment (ONBS) in patients undergoing SEG with pHDPE and concurrent LO.
Underrepresentation of Racial and Ethnic Minorities in Metastatic Colorectal Carcinoma Clinical Trials within the United States
Authors: Pu Tracey , Gustafson Alexandra , Luberice Kenneth , Akmal Sarfraz R. , Li Wei , Hernandez Jonathan M. , Blakely Andrew M. , Snyder Rebecca A. , Eng Oliver S.
Published: August 2024

Objective:

To investigate if underrepresentation of racial and ethnic minorities exists in metastatic colorectal carcinoma (CRC) clinical trials.

Summary Background Data:

Representation of vulnerable subpopulations is essential for generalizability of clinical trials. Limited studies to date have investigated racial and ethnic representation of patients enrolled in clinical trials for metastatic CRC.

Methods:

ClinicalTrials.gov was queried for metastatic CRC clinical trials in the United States from 2000-2020. Incidence data were extracted from the SEER Database. Enrollment fraction (EF) was defined as number of trial participants divided by U.S. incidence of metastatic CRC in each race, ethnicity, and gender. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of U.S. metastatic CRC incidence for each subgroup.

Results:

8084 patients from 135 clinical trials were analyzed. 49.6% of clinical trials reported race data and 34.8% reported ethnicity data. Compared to 2000-2009, 2010-2019 had increased representation data reporting for race (61.2% vs. 38.8%) and ethnicity (64.6% vs. 35.4%). Of trials with race data, White patients represented 77.0%, Black patients 6.6%, Asian/Pacific Islander (API) patients 16.1%, American Indian/Alaska Native (AIAN) patients 0.2%, and Hispanic patients 6.8%. Black patients (median RQ 0.54), API patients (median RQ 0.19), AIAN patients (median RQ 0.00), and Hispanic patients (median RQ 0.26) were underrepresented. Black patients had a higher degree of underrepresentation in clinical trials with serum creatinine inclusion criteria (RQ 0.40 vs. 0.86, P=0.034).

Conclusions:

Strategies are needed to increase minority enrollment in clinical trials for metastatic CRC. Identification of systemic barriers is integral in public policy advocacy to increase representation.
Neuro-Ophthalmic Manifestations of Adult Polyglucosan Body Disease
Authors: Dugue Andrew G. , Abreu Nicolas J. , Pillai Cinthi , Galetta Steven L. , Grossman Scott N.
Published: August 2024

Background:

Adult polyglucosan body disease (APBD) is caused by a deficiency in glycogen branching enzyme that leads to polyglucosan accumulation in multiple organs. It has a progressive clinical course with prominent neurologic manifestations. We aim to describe the neuro-ophthalmic manifestations of APBD.

Methods:

This is a case series of 3 individuals with genetically proven APBD. Written informed consent was provided by the brothers. We also performed a literature review on the current state of knowledge on APBD through PubMed.

Results:

Brother 1 developed gait imbalance and length-dependent polyneuropathy in his 40s followed by progressive urinary symptoms in his 50s. He reported diplopia and blurry vision in his 60s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy, convergence insufficiency, and a right fourth nerve palsy. Genetic testing showed a homozygous pathogenic variant in GBE1 c.986A>C p.Tyr329Ser. Brother 2 developed progressive urinary symptoms in his 40s that were followed by cognitive deficits, length-dependent polyneuropathy, and lower extremity weakness in his 50s and 60s. He reported blurred vision, and neuro-ophthalmic evaluation revealed bilateral optic neuropathy. Genetic testing revealed the same variant as Brother 1, GBE1 c.986A>C p.Tyr329Ser. Brother 3 developed progressive urinary urgency and lower extremity weakness in his 50s followed by a length-dependent polyneuropathy in his 60s. He reported diplopia and blurry vision in his 70s. Neuro-ophthalmic assessment revealed bilateral optic neuropathy and convergence insufficiency. Genetic testing revealed the same variant as Brothers 1 and 2, GBE1 c.986A>C p.Tyr329Ser.

Conclusions:

There is an array of afferent and efferent neuro-ophthalmic manifestations in APBD. Neuro-ophthalmic evaluation is crucial in evaluating and treating patients with APBD, particularly in those with visual dysfunction.
Identification of causative fungus from sterile abscess using metagenomics followed by in situ hybridization
Authors: Oki Hiroya , Niwa Ryotaro , Pranee Somboonthum , Motooka Daisuke , Onda Yoshiyuki , Nakata Jun , Nakajima Hiroko , Oka Yoshihiro , Sugiyama Haruo , Yoshii Yuka , Anzai Naoyuki , Nakamura Shota , Iida Tetsuya
Published: August 2024

Introduction. Invasive fungal infections require early diagnosis for treatment. Microscopic observation of biopsy and blood culture is the gold standard for the identification of the causative fungus, but it is difficult to identify the causative pathogen by a sterile abscess biopsy.

Case Presentation. We present a case report of breakthrough invasive trichosporonosis in a 65-year-old Japanese male with acute myeloid leukaemia receiving antifungal prophylaxis. Blood cultures showed no fungal growth, and a liver biopsy and a removed spleen with abscess showed fragmented fungi, but no fungal identification was possible. This report demonstrates that retrospective analyses were able to identify the causative fungus.

Conclusion. We narrowed down the candidate fungi by deep sequencing of the ITS1 region of fungal genome and confirmed that the fungus observed in the specimen was Trichosporon asahii by in situ hybridization using a DNA probe targeting 26S rRNA.
Genomic investigations of diverse corbiculate bee gut-associated Gilliamella reveal conserved pathways for energy metabolism, with diverse and variable energy sources
Authors: Nguyen Viet Hung
Published: August 2024

Gilliamella is a genus of bacteria commonly found as symbionts of corbiculate bees. Research into energy metabolism by this genus has predominantly been done through in vivo and in vitro experiments focused on the type species Gilliamella apicola. This study examined 95 publicly available genomes representing at least 18 Gilliamella species isolated predominantly from the hindgut of corbiculate bees. Energy metabolism pathways were found to be highly conserved across not only the Gilliamella but also other members of the family Orbaceae. Evidence suggests Gilliamella are capable of fermentation of both fumarate and pyruvate. Fermentation of the former produces succinate. Fermentation of the latter can produce acetate, ethanol, formate, and both isoforms of lactate for all Gilliamella and acetoin for some G. apicola strains. According to genomic evidence examined, all Gilliamella are only capable of respiration under microoxic conditions, while higher oxygen conditions likely inhibits respiration. Evidence suggests that the glycolysis and pentose phosphate pathways are essential mechanisms for the metabolism of energy sources, with the TCA cycle playing little to no role in energy metabolism for all Gilliamella species. Uptake of energy sources, i.e. sugars and derivatives, likely relies predominantly on the phosphoenol-pyruvate-dependent phosphotransferase system. Differences in the utilized energy sources may confer fitness advantages associated with specific host species.
Evaluating the Therapeutic Effects of Amino Acid Treatment on Vaso-Occlusive Pain in Sickle Cell Disease: A Systematic Review and Meta-Analysis Protocol
Authors: Zhang Bohan , Bubb Ciaran , Yao Sophie , Dong Vivian , Patel Priyal , Shahani Aanya , Lobner Katie , Badaki-Makun Oluwakemi
Published: August 2024

2

Introduction

Sickle Cell Disease (SCD) affects over 100,000 individuals in the United States and 20 million globally, causing acute and chronic pain. The disease is characterized by misshapen red blood cells caused by mutations in beta-hemoglobin genes. SCD leads to multiorgan damage, chronic anemia, and severe pain crises, with a median life expectancy of 43 years. Current treatments involve opioids, blood transfusions, and hydroxyurea. Amino acids, especially L-Glutamine, have shown promise in managing SCD pain. This systematic review aims to comprehensively analyze the effects of amino acid treatments on vaso-occlusive pain crises in SCD patients.

Methods

Following the Cochrane Handbook and PRISMA-P guidelines, this systematic review will include studies comparing amino acid treatment to placebo or standard care for SCD pain crises. Eligible studies of all age ranges, settings, and amino acid types will be considered. A comprehensive search strategy will be employed in PubMed, Embase, and Scopus databases. Studies will be assessed for risk of bias using Cochrane’s RoB2 tool. Primary outcomes include a reduction in pain, measured quantitatively through pain scales. Secondary outcomes encompass quality of life, hospital length of stay, and opioid equivalents used.

Discussion

Existing literature underscores the therapeutic potential of amino acids, yet there still lacks a systematic review comparing the overall effects of different amino acid treatments for vaso-occlusive crises in patients with SCD. This review aims to serve as a valuable resource for clinicians, offering insights into amino acid interventions as alternatives or supplements to opioid treatments. Additionally, it seeks to encourage further randomized clinical trials, contributing to an informed clinical use of amino acids for pain management in SCD. Ultimately, the findings aim to enhance the understanding of the therapeutic effects of essential amino acids on pediatric patients with SCD, facilitating evidence-based clinical decisions.
Phylogenetic proximity drives temporal succession of marine giant viruses in a five-year metagenomic time-series
Authors: Laperriere Sarah M. , Minch Benjamin , Weissman JL , Hou Shengwei , Yeh Yi-Chun , Cesar Ignacio-Espinoza J. , Ahlgren Nathan A. , Moniruzzaman Mohammad , Fuhrman Jed A.
Published: August 2024

Nucleocytoplasmic Large DNA Viruses (NCLDVs, also called giant viruses) are widespread in marine systems and infect a broad range of microbial eukaryotes (protists). Recent biogeographic work has provided global snapshots of NCLDV diversity and community composition across the world’s oceans, yet little information exists about the guiding ‘rules’ underpinning their community dynamics over time. We leveraged a five-year monthly metagenomic time-series to quantify the community composition of NCLDVs off the coast of Southern California and characterize these populations’ temporal dynamics. NCLDVs were dominated by Algavirales (Phycodnaviruses, 59%) and Imitervirales (Mimiviruses, 36%). We identified clusters of NCLDVs with distinct classes of seasonal and non-seasonal temporal dynamics. Overall, NCLDV population abundances were often highly dynamic with a strong seasonal signal. The Imitervirales group had highest relative abundance in the more oligotrophic late summer and fall, while Algavirales did so in winter. Generally, closely related strains had similar temporal dynamics, suggesting that evolutionary history is a key driver of the temporal niche of marine NCLDVs. However, a few closely-related strains had drastically different seasonal dynamics, suggesting that while phylogenetic proximity often indicates ecological similarity, occasionally phenology can shift rapidly, possibly due to host-switching. Finally, we identified distinct functional content and possible host interactions of two major NCLDV orders-including connections of Imitervirales with primary producers like the diatomChaetocerosand widespread marine grazers likeParaphysomonasand Spirotrichea ciliates. Together, our results reveal key insights on season-specific effect of phylogenetically distinct giant virus communities on marine protist metabolism, biogeochemical fluxes and carbon cycling.
Torsional Twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains
Authors: Rosas-Lemus Monica , Minasov George , Brunzelle Joseph S. , Taha Taha Y. , Lemak Sofia , Yin Shaohui , Shuvalova Ludmilla , Rosecrans Julia , Khanna Kanika , Seifert H Steven , Savchenko Alexei , Stogios Peter J. , Ott Melanie , Satchell Karla J. F.
Published: August 2024

Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge. We resolve the first complete x-ray structure of SARS-CoV SUD-N/M as well as a mutant variant of SARS-CoV-2 SUD-N/M modified to restore cysteines for interdomain disulfide bond naturally lost by evolution. Comparative analysis of all structures revealed SUD-N and SUD-M are not rigidly associated, but rather, have significant rotational flexibility. Phylogenetic analysis supports that the disulfide bond cysteines are also absent in pangolin-SARS and closely related viruses, consistent with pangolins being the presumed intermediate host in the emergence of SARS-CoV-2. The absence of these cysteines does not impact viral replication or protein translation.
Bibacillin 1: A two-component lantibiotic fromBacillus thuringiensis
Authors: Moreira Ryan , Yang Yi , Luo Youran , Gilmore Michael S. , van der Donk Wilfred
Published: August 2024

Here we describe bibacillin 1 – a two-component lantibiotic fromBacillus thuringiensis. The peptides that comprise bibacillin 1 are modified by a class II lanthipeptide synthetase Bib1M producing two peptides with non-overlapping ring patterns that are reminiscent of cerecidin and the short component of the enterococcal cytolysin (CylLS”), a virulence factor associated with human disease. Stereochemical analysis demonstrated that each component contains LL-methyllanthionine and DL-lanthionine. The mature bibacillin 1 peptides showed cooperative bactericidal activity against Gram-positive bacteria, including members of ESKAPE pathogens, and weak hemolytic activity. Optimal ratio studies suggest that bibacillin 1 works best when the components are present in a 1:1 ratio, but near optimal activity was observed at ratios strongly favouring one component over the other, suggesting that the two peptides may have different but complementary targets. Mechanism of action studies suggest a lipid II-independent killing action distinguishing bibacillin 1 from two other two-component lantibiotics haloduracin and lacticin 3147. One of the two components of bibacillin 1 showed cross reactivity with the cytolysin regulatory system. These result support the involvement of bibacillin 1 in quorum sensing and raise questions about the impact of CylLS”-like natural products on lanthipeptide expression in diverse bacterial communities.
Alzheimer’s disease protective allele ofClusterinmodulates neuronal excitability through lipid-droplet-mediated neuron-glia communication
Authors: Zhao Xiaojie , Li Yan , Zhang Siwei , Sudwarts Ari , Zhang Hanwen , Kozlova Alena , Moulton Matthew J. , Goodman Lindsey D. , Pang Zhiping P. , Sanders Alan R. , Bellen Hugo J. , Thinakaran Gopal , Duan Jubao
Published: August 2024

Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms remain largely unknown. For a strong AD-associated locus nearClusterin(CLU), we tied an AD protective allele to a role of neuronal CLU in promoting neuron excitability through lipid-mediated neuron-glia communication. We identified a putative causal SNP ofCLUthat impacts neuron-specific chromatin accessibility to transcription-factor(s), with the AD protective allele upregulating neuronalCLUand promoting neuron excitability. Transcriptomic analysis and functional studies in induced pluripotent stem cell (iPSC)-derived neurons co-cultured with mouse astrocytes show that neuronal CLU facilitates neuron-to-glia lipid transfer and astrocytic lipid droplet formation coupled with reactive oxygen species (ROS) accumulation. These changes cause astrocytes to uptake less glutamate thereby altering neuron excitability. Our study provides insights into how CLU confers resilience to AD through neuron-glia interactions.
Predicting microscale beat patterns from nanoscale chemomechanics in eukaryotic flagella
Authors: Cass James F. , Bloomfield-Gadêlha Hermes
Published: August 2024

We present quantitative predictions for experimental observables—amplitude, frequency and wavelength—of the eukaryotic flagellar beat in terms of underlying molecular chemomechanical parameters. Flagellar beating, an incompletely understood self-organized process arising from the collective action of dynein molecular motors, is modelled as a reaction-diffusion (RD) system with an oscillatory instability arising from motor-induced microtubule sliding. While the RD model accurately reproduces beating patterns of bull spermatozoa andC. Reinhardtii, existing linear analyses and simulations are unable to provide a complete framework for understanding nonlinear waveform formation. Here, we derive analytical expressions that reveal the nonlinear dependence of beat characteristics on parameters such as motor binding duty ratio, stepping velocity, and axonemal resistance. Our analysis uncovers a novel out-of-equilibrium mechanism for base-to-tip wave propagation, involving an interference pattern between unstable standing wave modes that generates travelling waves. Predicted beat patterns agree remarkably with numerical simulations, even far from the critical point marking the onset of oscillations. This unveils key molecular parameters that govern oscillation initiation, amplitude saturation, frequency shifts, and the spatial phase gradient crucial for generating propulsive hydrodynamic force. Our results yield biophysical understanding of how molecular interactions shape flagellar beating patterns, allowing for the inference of molecular properties from macroscopic observations. This challenges existing hypotheses on wave generation and demonstrates the power of nonlinear analysis to uncover new phenomena beyond the reach of linear models and computational studies alone.
Inferring replication states of bacteria and viruses in enrichment cultures via long-read sequencing
Authors: Simon Sophie A. , Soares Andre , Bornemann Till L.V. , Lange Adrian , Griesdorn Lea , Fuentes Adrian , Dieckmann Marie , Krok Beate , Ruff S. Emil , Hugler Michael , Moraru Cristina , Probst Alexander J
Published: August 2024

Most microorganisms cannot be cultured in isolation, necessitating sophisticated methods for studying their (eco)physiology. While numerous approaches can probe the activity of given microbes in enrichment cultures, no single technique can render simultaneous data on both metabolic capacities and mobile genetic elements. Here, we apply long-read sequencing to monitor the incorporation of non-canonical bases in genome-resolved metagenomic datasets and elucidate the replication patterns of both bacteria and phages. This technology enables the simultaneous reconstruction of both prokaryotic and viral genomes (alongside genomics downstream analyses like metabolic predictions), in addition to providing information regarding their replication in enrichment cultures. By spiking the base analog 5-bromo-2'-deoxyuridine (BrdU) into activated sludge microcosms, we determined that 114 of the 118 high-quality genomes recovered were actively replicating in enrichment cultures from activated sludge and identified both slow (low BrdU incorporation and change in abundance) and rapidly replicating organisms (high BrdU incorporation and change in abundance). Some of the genomes detected exhibited regions rich in BrdU that were predicted to represent prophages in their lytic cycle. Ultimately, this novel means of monitoring the replication responses of microbes, and deciphering their genomes and active mobile genetic elements will advance and empower strategies aimed at isolating previously uncultivated microbes in pure culture.
Conserved role of the SERK–BIR module in development and immunity across land plants
Authors: Yan Yijia , Mellüh Jaqueline , Mecchia Martin A. , Jeon Hyung-Woo , Melkonian Katharina , Holzberger Clemens , Harzen Anne , Stolze Sara Christina , Franzen Rainer , Hirakawa Yuki , Delgado Ana I. Caño , Nakagami Hirofumi
Published: August 2024

SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs), which are subfamily II of leucine-rich repeat receptor-like kinases (LRR-RLKs), play diverse roles in development and immunity in the angiospermArabidopsis thaliana. AtSERKs act as co-receptors for many LRR-RLKs, including BRASSINOSTEROID INSENSITIVE 1 (BRI1) and FLAGELLIN SENSITIVE 2 (FLS2).1–4The conserved tyrosine (Y) residue in AtSERK3 is crucial for signaling specificity in differentiating BRI1- and FLS2-mediated pathways.5BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1)-INTERACTING RECEPTOR-LIKE KINASES (BIRs) interact with SERKs under resting conditions, negatively regulating SERK-mediated pathways.6,7SERK and BIR are highly conserved in land plants, whereas BRI1 and FLS2 homologs are absent or poorly conserved in bryophyte lineages.8,9The biological functions of SERK homologs in non-flowering plants are largely unknown. The genome of the liverwortMarchantia polymorphaencodes single homologs for SERK and BIR, namely MpSERK and MpBIR.9We here show that Mpserkdisruptants display growth and developmental defects with no observable sexual or vegetative reproduction. Complementation analysis revealed a contribution of the conserved Y residue of MpSERK to growth. Proximity labelling-based interactomics identified MpBIR as a MpSERK interactor. Mpbirdisruptants displayed defects in reproductive organ development. Patterns of development- and immunity-related gene expression in Mpserkand Mpbirwere antagonistic, suggesting that MpBIR functions as a MpSERK repressor. The pathogenic bacteriumPseudomonas syringaepv.tomatoDC3000 grew poorly on Mpbir, indicating a significant role of the MpSERK1MpBIR module in immunity. Taken together, we propose that the SERK–BIR functional module was already regulating both development and immunity in the last common ancestor of land plants.
Machine learning reveals genes impacting oxidative stress resistance across yeasts
Authors: Aranguiz Katarina , Horianopoulos Linda C. , Elkin Logan , Abá Kenia Segura , Wrobel Russell L. , Shiu Shin-Han , Rokas Antonis , Hittinger Chris Todd
Published: August 2024

Reactive oxygen species (ROS) are highly reactive molecules encountered by yeasts during routine metabolism and during interactions with other organisms, including host infection. Here, we characterized the variation in resistance to ROS across the ancient yeast subphylum Saccharomycotina and used machine learning (ML) to identify gene families whose sizes were predictive of ROS resistance. The most predictive features were enriched in gene families related to cell wall organization and included two reductase gene families. We estimated the quantitative contributions of features to each species’ classification to guide experimental validation and showed that overexpression of the old yellow enzyme (OYE) reductase increased ROS resistance inKluyveromyces lactis, whileSaccharomyces cerevisiaemutants lacking multiple mannosyltransferase-encoding genes were hypersensitive to ROS. Altogether, this work provides a framework for how ML can uncover genetic mechanisms underlying trait variation across diverse species and inform trait manipulation for clinical and biotechnological applications.
Visualization and analysis of medically relevant tandem repeats in nanopore sequencing of control cohorts with pathSTR
Authors: De Coster Wouter , Höijer Ida , Bruggeman Inge , D'Hert Svenn , Melin Malin , Ameur Adam , Rademakers Rosa
Published: August 2024

The lack of population-scale databases hampers research and diagnostics for medically relevant tandem repeats and repeat expansions. We attempt to fill this gap using our pathSTR web tool, which leverages long-read sequencing of large cohorts to determine repeat length and sequence composition in a healthy population. The current version includes 1040 individuals of The 1000 Genomes Project cohort sequenced on the Oxford Nanopore Technologies PromethION. A comprehensive set of medically relevant tandem repeats has been genotyped using STRdust and LongTR to determine the tandem repeat length and sequence composition. PathSTR provides rich visualizations of this data set and the feature to upload one's data for comparison along the control cohort. We demonstrate the implementation of this application using data from targeted nanopore sequencing of a patient with myotonic dystrophy type 1. This resource will empower the genetics community to get a more complete overview of normal variation in tandem repeat length and sequence composition and, as such, enable a better assessment of rare tandem repeat alleles observed in patients.