bluuebunny/crossref_metadata_2025 huggingface dataset:
The hydrodynamic response of small-scale structure to reionization drives large IGM temperature fluctuations that persist to z = 4
Authors: Cain Christopher , Scannapieco Evan , McQuinn Matthew , D’Aloisio Anson , Trac Hy
Published: July 2024

The thermal history and structure of the intergalactic medium (IGM) at $z \ge 4$ is an important boundary condition for reionization, and a key input for studies using the Ly $\alpha$ forest to constrain the masses of alternative dark matter candidates. Most such inferences rely on simulations that lack the spatial resolution to fully resolve the hydrodynamic response of IGM filaments and minihaloes to H i reionization heating. In this letter, we use high-resolution hydrodynamic + radiative transfer simulations to study how these affect the IGM thermal structure. We find that the adiabatic heating and cooling driven by the expansion of initially cold gas filaments and minihaloes sources significant small-scale temperature fluctuations. These likely persist in much of the IGM until $z \le 4$. Capturing this effect requires resolving the clumping scale of cold, pre-ionized gas, demanding spatial resolutions of ${\le} 2$ $h^{-1}$kpc. Pre-heating of the IGM by X-rays can slightly reduce the effect. Our preliminary estimate of the effect on the Ly $\alpha$ forest finds that, at $\log (k /[{\rm km^{-1} s}]) = -1.0$, the Ly $\alpha$ forest flux power (at fixed mean flux) can increase ${\approx} 10~{{\ \rm per\ cent}}$ going from 8 and 2 $h^{-1}$kpc resolution at $z = 4{\!-\!}5$ for gas ionized at $z \ \lt\ 7$. These findings motivate more careful analyses of how the effects studied here affect the Ly $\alpha$ forest.
Upper limit on the coronal cosmic ray energy budget in Seyfert galaxies
Authors: Inoue Yoshiyuki , Takasao Shinsuke , Khangulyan Dmitry
Published: July 2024

The IceCube Collaboration has reported possible detections of high-energy neutrinos from nearby Seyfert galaxies. While central hot coronae are proposed as the primary neutrino production site, the exact coronal cosmic ray energy budget has been loosely constrained. In this study, we propose a new stringent upper bound on the coronal cosmic ray energy budget of Seyfert galaxies, considering both accretion dynamics and observed properties of radio-quiet Seyfert galaxies. Notably, even under the calorimetric condition where cosmic rays lose all their energy, our limit indicates that the coronal neutrino flux of NGC 1068 is about an order of magnitude fainter than the observed levels. This discrepancy suggests the need for further theoretical and observational investigations on the IceCube signals from Seyfert galaxies.
The intron binding protein EMB-4 is an opposite regulator of cold and high temperature tolerance in Caenorhabditis elegans
Authors: Ohta Akane , Sato Yuki , Isono Kazuho , Kajino Takuma , Tanaka Keisuke , Taji Teruaki , Kuhara Atsushi
Published: July 2024

Adaptation and tolerance to changes in heat and cold temperature are essential for survival and proliferation in plants and animals. However, there is no clear information regarding the common molecules between animals and plants. In this study, we found that heat, and cold tolerance of the nematode Caenorhabditis elegans is oppositely regulated by the RNA-binding protein EMB-4, whose plant homolog contains polymorphism causing heat tolerance diversity. Caenorhabditis elegans alters its cold and heat tolerance depending on the previous cultivation temperature, wherein EMB-4 respectively acts as a positive and negative controller of heat and cold tolerance by altering gene expression. Among the genes whose expression is regulated by EMB-4, a phospholipid scramblase, and an acid sphingomyelinase, which are involved in membrane lipid metabolism, were found to play essential roles in the negative regulation of heat tolerance.
Deformity Considerations in Cervical Laminoplasty
Authors: Drain Joseph P. , Alvarez Paul , Spiker William Ryan , Yu Elizabeth
Published: July 2024

Objectives:

We discuss the incidence of postoperative kyphosis following laminoplasty and its impact on outcomes, as well as critical radiographic parameters, intraoperative technical factors, and postoperative protocols that can be used to improve results.

Summary of Background Data:

When appropriately selected, cervical laminoplasty is a motion-sparing treatment option for cervical myelopathy and is a valid alternative to laminectomy and fusion procedures. However, like other posterior-based cervical decompression techniques, laminoplasty can cause postoperative kyphosis.

Methods:

A PubMed search was performed to gather articles that focus on cervical deformity in the context of cervical laminoplasty.

Results:

The reported conversion rates of lordotic to kyphotic cervical alignment after laminoplasty range from 5.2% to 11.3%. Kyphosis likely reduces the benefit from the operation as measured by postoperative mJOA scores. A surgeon can minimize the risk of causing a clinically significant reduction in lordosis by screening out patients with certain radiographic characteristics. Intraoperative decisions such as dissection techniques, levels chosen, and hybrid constructs can preserve the cervical tension band. Certain postoperative protocols can improve cervical posture.

Conclusions:

Cervical laminoplasty is an effective tool for treating degenerative cervical myelopathy. Careful radiographic screening, intraoperative decision-making, and postoperative protocols can minimize the development of postoperative cervical deformity and improve outcomes.

Level of Evidence:

Level V.
The Role of Negative Pressure Wound Therapy in Temporizing Traumatic Wounds before Lower Limb Soft Tissue Reconstruction: A Systematic Review
Authors: Barone Natasha , Ziolkowski Natalia , Haykal Siba
Published: July 2024

Background:

In practice, there is often a delay from initial debridement and temporary fixation to definitive soft tissue coverage of traumatic leg wounds. Without clear evidence, conservative negative pressure wound therapy (NPWT) is increasingly used to temporize these wounds. This systematic review summarizes and synthesizes the literature on using NPWT to temporize traumatic leg wounds before surgery in adult surgical patients.

Methods:

A comprehensive search of Medline, Embase, and Cochrane Library was performed from inception until July 2022, inclusively. Two independent reviewers performed screening, data extraction, and risk of bias assessment. Primary English studies, including adult patients (≥16 years old) with a fracture below the knee up to and including the ankle that received NPWT to temporize wounds before definitive soft tissue reconstruction with a flap and/or graft, were included.

Results:

Thirty-four studies, including 804 patients who received NPWT, were included. The partial/total flap loss rate was 6.95% (n = 9 studies), the infection rate was 19.5% (n = 25 studies), the nonunion rate was 18% (n = 15 studies), the delayed union rate was 9.31% (n = 3 studies), and the amputation rate was 15.4% (n = 6 studies). The mean late stay was 43.1 days (n = 9 studies), and the follow-up length was 23.7 months (n = 9 studies). The mean time to wound healing was 5.63 months (n = 2 studies), and the time to soft tissue coverage was 40.8 days (n = 12 studies). The mean time to achieve bone union was 7.26 months (n = 6 studies).

Conclusion:

NPWT can be used to temporize traumatic wounds while awaiting soft tissue reconstruction.
Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitis
Authors: Yuan Qiaoping , Hodgkinson Colin , Liu Xiaochen , Barton Bruce , Diazgranados Nancy , Schwandt Melanie ,   with DASH, InTEAM, SCAHC, TREAT and Alcohol Hepatitis Genomics consortia, Morgan Timothy , Bataller Ramon , Liangpunsakul Suthat , Nagy Laura E. , Goldman David
Published: July 2024

Background and Aims:

Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder. Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study aims to identify genes and genetic variations that contribute to the development of AH.

Approach and Results:

Exome-sequencing of patients with AH (N=784) and heavy drinking controls (N=951) identified an exome-wide significant association for AH at patalin-like phospholipase domain containing 3, as previously observed for AC in genome-wide association study, although with a much lower effect size. Single nucleotide polymorphisms (SNPs) of large effect size at inducible T cell costimulatory ligand (ICOSLG) (Chr 21) and TOX4/RAB2B (Chr 14) were also exome-wide significant. ICOSLG encodes a co-stimulatory signal for T-cell proliferation and cytokine secretion and induces B-cell proliferation and differentiation. TOX high mobility group box family member 4 (TOX4) was previously implicated in diabetes and immune system function. Other genes previously implicated in AC did not strongly contribute to AH, and the only prominently implicated (but not exome-wide significant) gene overlapping with alcohol use disorder was alcohol dehydrogenase 1B (ADH1B). Polygenic signals for AH were observed in both common and rare variant analysis and identified genes with roles associated with inflammation.

Conclusions:

This study has identified 2 new genes of high effect size with a previously unknown contribution to alcohol-associated liver disease and highlights both the overlap in etiology between liver diseases and the unique origins of AH.
NATURAL COURSE OF AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT
Authors: Su Yongyue , Wen Feng , Gan Yuhong , Zeng Yunkao , Zhuang Xuenan , He Guiqin , Zhang Yining , Yang Ruijun , Zhang Xiongze
Published: July 2024

Purpose:

Retentional pigment epithelial detachment (PED) associated with age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) is hypothesized to be caused by Bruch membrane's lipid barrier. This study aimed to report the natural course of retentional PED and evaluate the relationship between retentional PED evolution and ASHS-LIA.

Methods:

Patients with treatment-naïve retentional PED were enrolled and observed every 3 months for at least 12 months. Treatment was not performed except for secondary macular neovascularization.

Results:

In 55 studied eyes with a median follow-up of 18.0 (range: 12–36) months, 87.3% (48/55) of the retentional PEDs persisted, 7.3% (4/55) resolved, and 5.5% (3/55) progressed to polypoidal choroidal vasculopathy. The mean PED area significantly increased during the follow-up (P < 0.001) and with the ASHS-LIA grade at each follow-up point (all P <0.05), especially during the first 6 months before approaching the edge of confluent ASHS-LIA. Persistent PEDs were mostly stable (52.1%) or enlarged (45.8%) but reduced in only 1 case (2.1%) because of retinal pigment epithelium microrip at the edge of PED. The persistent PEDs were all within the ASHS-LIA region, especially the macular confluence region. The resolved PEDs all had grade 1 ASHS-LIA and resolved after gradual expansion of PED beyond the confluent ASHS-LIA region. Pigment epithelial detachments that progressed to macular neovascularization all had confluent grade 2 or 3 ASHS-LIA. Retinal pigment epithelium microrips or apertures within PED did not affect the progression of the PED.

Conclusion:

The natural course of retentional PED is closely related to the features of ASHS-LIA and supports its lipid-barrier hypothesis.
Severe Circulatory Disturbance in Optic Disc, Retina, and Choroid Following Sub-Tenon Triamcinolone Acetonide Injection for Posterior Scleritis
Authors: Akada Masahiro , Muraoka Yuki , Morooka Satoshi , Ishihara Kenji , Hata Masayuki , Tsujikawa Akitaka
Published: July 2024

Purpose:

To report a rare case of optic disc and chorioretinal vascular occlusions in the right eye following sub-Tenon injection of triamcinolone acetonide (STTA) in an older male patient with scleritis and to discuss the associated risk factors and potential alternative therapies.

Methods:

The medical history and clinical examination, including fundoscopy, fluorescein angiography (FA), and indocyanine green angiography (ICGA), were conducted to diagnose and evaluate the extent of vascular occlusion after STTA. An extensive literature review was undertaken to ascertain the associated risks and consider other treatment options for scleritis.

Results:

Severe circulatory disturbances in the optic disc and chorioretinal regions of the right eye developed after STTA for exacerbated scleritis, as confirmed by FA and ICGA, resulting in a significant decrease in visual acuity. A complex medical history encompassing ophthalmic and systemic health issues may have contributed to this negative outcome. A literature review pointed out the potential complications of STTA and highlighted alternative approaches to scleritis management.

Conclusions:

Cautious application of STTA in treating scleritis is crucial, especially in patients with pre-existing vascular or ocular conditions. Thus, a multidisciplinary approach and a careful assessment of various treatment options are vital to minimize the risk of severe complications and improve patient outcomes.
Evaluation of Host Gene Methylation as a Triage Test for HPV–Positive Women—A Cohort Study
Authors: Vieira-Baptista Pedro , Costa Mariana , Hippe Juliane , Sousa Carlos , Schmitz Martina , Silva Ana-Rita , Hansel Alfred , Preti Mario
Published: July 2024

Objectives

This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance.

Materials and Methods

Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice.

Results

The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1–71.6%) and 88.4% (83.2–92.5%), respectively. For CIN3+, it was of 78.0% (64.0–88.5%) and 86.0% (80.8–90.2%), respectively.

The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%.

The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel.

Conclusions

The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.
Development of Fournier’s gangrene after chemotherapy for the recurrence of testicular cancer despite the absence of anorectal lesions: A case report
Authors: Nonaka Kenichi , Kawase Kota , Takagi Kimiaki , Takatsu Yuta , Maniwa Koji , Takao Chika , Komura Minoru , Mushika Yoshinori , Takeuchi Noriyuki , Kato Toshio , Kusakabe Mitsuhiko , Kondo Mitsutaka
Published: July 2024

Background:

Fournier’s gangrene usually occurs when a specific bacterium intrudes into soft tissue, causing a wound or tumor. We encountered a patient with Fournier’s gangrene due to severe myelosuppression after chemotherapy, despite the absence of an initial lesion on the anus and rectum.

Case presentation:

A 54-year-old man with a left testicular cancer recurrence had undergone chemotherapy. He had asymptomatic hepatitis and high hepatitis B virus DNA levels, which were normalized by administering tenofovir alafenamide fumarate. Twelve days after the start of chemotherapy, he complained of severe pain around the anus. The following day, he went into septic shock. Visual inspection showed dark purple skin discoloration on the left side of the anus. Laboratory data revealed severe neutropenia. Computed tomography showed a high density of soft tissue on the left side of the anus and gas bubbles in the left femoral ring. We diagnosed the patient with Fournier’s gangrene due to a severe immunosuppressive state resulting from chemotherapy. We emergently removed necrotic tissue to the fullest extent possible. However, because the patient was in severe sepsis status, careful management in the intensive care unit was required for 32 days. After the first emergency operation, we performed several additional excisions. Finally, 391 days after the initial surgery, the patient was discharged from our hospital. The tumor has not recurred, and he is under outpatient observation in the urology department.

Conclusion:

Fournier’s gangrene should be considered in patients who are in a severe myelosuppressive state due to chemotherapy, have normal hepatitis B virus DNA levels but high hepatitis B surface antigen after tenofovir administration, complain of severe pain in the perianal area, and have a dark purple skin discoloration around the anus, despite having no initial anorectal lesions.
Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report
Authors: Lee Hyeonjeong , Yang Jaeseok , Kwon Jinykung , Heo Mihwa , Kim Yaerim , Paek Jin Hyuk , Shin Hyeongchan , Choe Misun , Han Seungyeup , Jin Kyubok
Published: July 2024

Rationale:

Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma.

Patient concerns:

A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain.

Diagnoses and Interventions:

Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient’s performance status, we initiated low-dose steroid pulse therapy, followed by conservative management.

Outcomes:

While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis.

Lessons:

This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation.
Pulmonary artery air embolism with consequent primary respiratory alkalosis and secondary metabolic alkalosis following ventilation therapy: A case report
Authors: Altorbak Nora A. , Daghistani Rayyan A. , Al-Omaish Hassan R. , Alsaab Thamer A. , Alhomaiani Shahad K.
Published: July 2024

Background:

An air embolism is a rare complication that occurs after air enters blood vessels, causing almost no to mild symptoms in patients. Although uncommon, air embolism can be deadly. Critical care professionals should know the warning signs of air embolism and be prepared to carry out the necessary therapeutic interventions. To reduce morbidity and death, this clinical condition must be identified early. Here we are presenting a case of pulmonary artery air embolism as a consequence of contrast agent injection in a chest computed tomography study.

Case presentation:

A 70-year-old male patient were presented with pulmonary artery air embolism as a consequence of contrast agent injection in a chest computed tomography study. The patient experienced worsening respiratory symptoms that necessitated oxygen therapy, which resulted in respiratory alkalosis with secondary metabolic alkalosis. Following removal of the BiLevel positive airway pressure, the patient was switched to a 2-L nasal cannula, and his breathing rate increased to 34 breaths/min. After 8.5 hours of monitoring the patient’s vital signs, the nasal cannula was removed, and the patient began breathing room air on his own. His vital signs then stabilized and arterial blood gas parameters returned to normal. The patient’s condition improved, and he was discharged from the hospital after 9 days. Due to a high level of cytomegalovirus, the discharge prescriptions included valganciclovir film-coated tablets (900 mg, oral BID every 12 hours for 30 days) and apixaban (5 mg BID). The patient was then monitored at the outpatient clinic.

Conclusion:

Although rare, an air embolism can cause minor symptoms if it is small in volume or can be fatal if large. After contrast-enhanced radiological studies, physicians should be aware of any signs of respiratory distress or worsening of symptoms in their patients. Additionally, patients should be mindful of the potential complications associated with ventilation therapy.
Hormone receptor expression in low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma: A case report
Authors: Leng Lei , Hua Xin , Liu Wei , Jian Wu
Published: July 2024

Rationale:

Breast low-grade adenosquamous carcinoma is an uncommon cancer that has been neglected in genetic and pathophysiological research. Consequently, medical practitioners face challenges in the effective diagnosis and treatment of this condition.

Patient concerns:

We present the case of a 57-year-old Asian female patient who presented with bilateral breast masses on physical examination. Ultrasound and an MRI revealed a highly suspicious malignant mass in her right breast that was completely removed surgically.

Diagnoses:

After pathological analysis, the diagnosis was low-grade adenosquamous carcinoma with local high-grade transformation, and some of the tumor components were estrogen receptor positive.

Interventions:

The patient underwent appropriate postoperative chemotherapy and achieved a favorable outcome.

Outcomes:

During the follow-up period after surgical resection, the patient did not experience any local recurrence or distant metastasis.

Lessons:

Owing to the rare combination of estrogen receptor positivity and high-grade progression, this patient also required adjuvant chemotherapy. This enhances the essential foundation for diagnosing and treating this rare disease, and facilitates the implementation of treatment plans.
Genetic Heterogeneity, Craniofacial Surgical Burden, and Surgical Techniques in Patients With Saethre-Chotzen Syndrome
Authors: Romeo Dominic J. , Oral Kaan T. , Massenburg Benjamin B. , Ng Jinggang J. , Wu Meagan , Sussman Jonathan H. , Du Steven , Bartlett Scott P. , Swanson Jordan W. , Taylor Jesse A.
Published: July 2024

Objective:

While genotype correlates with phenotype in patients with many forms of syndromic craniosynostosis, the relationship between molecular diagnosis and craniofacial surgical history in patients with Saethre-Chotzen syndrome (SCS) is more variable. This manuscript characterizes that relationship and evaluates operative trends in these patients over the past 3 decades.

Methods:

Demographic information, molecular diagnosis, and craniofacial surgical history in patients born with SCS between 1989 and 2023 were compared with appropriate statistics, including t tests and analysis of variance.

Results:

Thirty-five patients with SCS were included, and there was no difference in total craniofacial procedures among those with TWIST1 substitutions (2.1 ± 1.6), duplications (3.0 ± 4.2), insertions (3.5 ± 0.7), or deletions (2.4 ± 1.9; P = 0.97). Cranial expansion rates were also similar across all genetic diagnoses (P>0.05), and surgical incidence was similar across patients with unicoronal, bicoronal, and multisuture involvement (P > 0.05). Those with an initial fronto-orbital advancement had a lower incidence of secondary cranial vault procedures compared with those with an initial posterior vault distraction osteogenesis (29% versus 71%, P < 0.05), though this did not control for phenotypic severity. On average, total cranial vault surgical burden (1.35 ± 0.67 versus 1.75 ± 0.46) and cranial expansion surgical burden (1.40 ± 0.68 versus 1.88 ± 0.64) between the fronto-orbital advancement–first and posterior vault distraction osteogenesis–first cohorts were similar (P = 0.11, P = 0.17, respectively).

Conclusion:

While SCS is molecularly and phenotypically heterogeneous, genetic diagnosis does not appear associated with rates of craniofacial surgery. Additional prospective study of correlations between genotype, severity of craniofacial manifestations, and treatment algorithms is warranted; but, in the end, it may be that this highly variable form of syndromic craniosynostosis warrants tailored, expectant management.
Comparison of Endoscopic Ultrasound-guided Cyanoacrylate Injection and Transjugular Intrahepatic Portosystemic Shunt in the Prevention of Gastric Varices Rebleeding
Authors: Zeng Zhuang , Wang Zhihong , Jin Jing , Zhang Fumin , Zhang Qianqian , Mei Xuecan , Kong Derun
Published: July 2024

Objective:

The purpose of this study was to investigate the efficacy and safety of endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) and transjugular intrahepatic portal shunts (TIPSs) in the treatment of patients with cirrhosis with ruptured gastric varices.

Methods:

In this retrospective study, 105 patients with liver cirrhosis and gastric varicose veins who were admitted to the First Affiliated Hospital of Anhui Medical University between April 2018 and April 2023 without nonselective β-blockers treatment and no portal vein thrombosis were evaluated. The patients were divided into the transjugular intrahepatic portal shunt (TIPS) group (n = 60) and the EUS-CYA group (n = 45) for the purpose of evaluating postoperative rebleeding rates, complications, survival rates, and other factors.

Results:

During the follow-up, there was no significant difference in the rebleeding rates between the TIPS group and EUS-CYA group within 3 months (5% vs 2.2%; P = 0.825; 10% vs 20%, P = 0.147). However, the TIPS group had significantly lower rebleeding rates than the EUS-CYA group at 6 months (10% vs 33.3%; P = 0.030) and 1 year or longer (11.7% vs 42.2%; P < 0.01). In terms of hepatic encephalopathy, the incidence rate of the TIPS group was significantly higher than that of the EUS-CYA group (20% vs 2.2%; P = 0.006). In addition, there was no difference in the survival rates between the two groups (93.3% vs 97.8%; P = 0.552).

Conclusions:

TIPS is superior to EUS in preventing rebleeding in patients with ruptured varices of the fundus, but it has a higher incidence of hepatic encephalopathy, and there is no difference in long-term survival between the two groups.
Viral-bacterial codetection among patients with pneumonia during the COVID-19 pandemic in Jakarta, Indonesia
Authors: Wiyatno Ageng , Myint Khin Saw , Artika I Made , Soebandrio Amin , Safari Dodi
Published: July 2024

We determined the prevalence of viral-bacterial codetection among SARS-CoV-2 suspected patients with pneumonia admitted to the health care facilities in Jakarta, Indonesia. Of the 245 pneumonia cases, 72 (29%) were confirmed positive for SARS-CoV-2. Among other viruses, paramyxovirus was the predominant virus identified (7%) followed by herpesvirus (6%) and influenza virus (4%). Bacterial screening of nasopharyngeal swab specimens detected 21 (9%) and 14 (6%) positive for Haemophilus influenzae and Streptococcus pneumoniae respectively. Overall, the higher rate of viral-bacterial codetection was observed in the SARS-CoV-2 positive cases than in the negative cases.
Flavobacterium facile sp. nov., isolated from water system of Atlantic salmon (Salmo salar) fry cultured in Chile
Authors: Irgang Rute , Saldarriaga-Córdoba Mónica , Poblete-Morales Matías , Avendaño-Herrera Ruben
Published: July 2024

Strain T-12T, an orange, Gram-stain-negative, non-motile, rod-shaped strain, was isolated in November 2013 from water samples collected from an Atlantic salmon (Salmo salar) fry culturing system at a fish farm in Chile. Phylogenetic analysis based on 16S rRNA sequences (1394 bp) revealed that strain T-12T belonged to the genus Flavobacterium, showing close relationships to Flavobacterium bernardetii F-372T (99.48 %) and Flavobacterium terrigena DS-20T (98.50 %). The genome size of strain T-12T was 3.28 Mb, with a G+C content of 31.1 mol%. Genome comparisons aligned strain T-12T with Flavobacterium bernardetii F-372T (GCA_011305415) and Flavobacterium terrigena DSM 17934T (GCA_900108955). The highest digital DNA–DNA hybridization (dDDH) values were 42.6 % with F. bernardetii F-372T (GCA_011305415) and 33.9 % with F. terrigena DSM 17934T (GCA_900108955). Pairwise average nucleotide identity (ANI) calculations were below the species cutoff, with the best results with F. bernardetii F-372T being: ANIb, 90.33 %; ANIm, 91.85 %; and TETRA, 0.997 %. These dDDH and ANI results confirm that strain T-12T represents a new species. The major fatty acids were iso-C15 : 0 and C15 : 1ω6с. Detected polar lipids included phospholipids (n=2), aminophospholipid (n=1), aminolipid (n=1) and unidentified lipids (n=2). The predominant respiratory quinone was menaquinone MK7 (80 %) followed by MK-6 (20 %). Phenotypic, chemotaxonomic, and genomic data support the classification of strain T-12T (=CECT 30410T=RGM 3222T) as representing a novel species of Flavobacterium, for which the name Flavobacterium facile sp. nov. is proposed.
Fragile X Syndrome Carrier Screening Using a Nanopore Sequencing Assay
Authors: Xia Zhongmin , Deng Qiuxiao , Hu Ping , Gao Chunliu , Jiang Yu , Zhou Yulin , Guo Qiwei
Published: July 2024

BACKGROUND

Fragile X syndrome (FXS) is the leading cause of monogenic autism spectrum disorder and inherited intellectual disabilities. Although the value of population-based FXS carrier screening has been acknowledged, appropriate screening methods are urgently required to establish and implement screening programs.

METHODS

We developed a nanopore sequencing-based assay that includes data analysis software to identify FXS carriers. Reference and clinical samples were used to evaluate the performance of our nanopore sequencing assay. Triplet-primed PCR and PacBio long-read sequencing were used for comparisons.

RESULTS

Nanopore sequencing identified reference carrier samples with a full range of premutation alleles in single-, 10-, and 100-plex assays, and identified AGG interruptions in an allele-specific manner. Nanopore sequencing revealed no size preference for amplicons containing different length CGG repeat regions. Finally, nanopore sequencing successfully identified three carriers among ten clinical samples for preliminary clinical validation. The observed variation in CGG repeat region size resulted from the base-calling process of nanopore sequencing.

CONCLUSIONS

Our nanopore sequencing assay is rapid, high-capacity, inexpensive, and easy to perform, thus providing a promising tool and paving the way for population-based FXS carrier screening.
Biological Systematic of the genusNotodiaptomusKiefer 1936 (Copepoda: Calanoida)
Authors: Geraldes-Primeiro Luis , Cavalcanti Mauro J. , Santos-Silva Edinaldo N.
Published: July 2024

The present effort is a systematic review of the most diverse diaptomid copepods from the South America, theNotodiaptomusKiefer 1936. We proposed to review and identify new morphological characteristics for 37 currently accepted species, assess nomenclatural status, and to examine their relatedness relations. The identification of 2700 morphological hypotheses for males and females are encoded in DEscription Language for TAxonomy (DELTA), used for a historical evaluation of the genus, and arrive at the first parsimony-based phylogeny forNotodiaptomus. We present synonymy of all species, status of type material, updated record of occurrences, taxonomic remarks, and dichotomous and interactive key for males and females. The rescue of the common and exclusive ancestor based on 80 synapomorphic characters recovers the monophyly of the organisms of the considered species, supports the discussion of the exclusive conditions and the historically indicated taxonomic relationships. Through this we wish to help establish an additional step on the consistency of the taxonomy of these species, contributing to answer important questions about the origin of some of the characteristics presented.
Weathering the storm for love: Mate searching behaviour of wild males of the Sydney funnel-web spider (Atrax robustus)
Authors: Creak Caitlin N. , Muirhead Hugo , Kasumovic Michael , Bonduriansky Russell , Buzatto Bruno A.
Published: July 2024

The risky business of mate-searching often leaves the actively searching sex facing threats and rapidly changing conditions. Yet, active mate-searching behaviour is rarely studied in invertebrates, and we have limited understanding of how mate-searching strategies have evolved to cope with risks posed by harsh weather. We investigated how mate-searching males move through their habitat and how their movement is affected by weather conditions in the Sydney funnel-web spider (Atrax robustus), one of the world’s most venomous spiders. As is common in mygalomorphs spiders, females are functionally sessile, and are thought to spend their whole lives in a single burrow, whereas males must permanently abandon their burrows to mate during the breeding season. Nineteen male spiders were fitted with micro-radio transmitters and tracked during their mating seasons in 2020 (n = 2), 2021 (n = 8) and 2022 (n = 9) in Lane Cove National Park, in Sydney, Australia. Males moved at night, typically in a zig-zag pattern, and were found in new locations on approximately 50% of daily resighting’s. Males often spent several days in a female’s burrow, and some female burrows were visited by multiple males. When outside a female’s burrow, males constructed and occupied temporary shelters (‘temporacula’). Males were most likely to move and/or moved furthest when there was no rain, and on warm nights after cool days. Our findings suggest that mate-searchingA. robustusmales prefer to search for females in less risky conditions, revealing novel risk-minimizing strategies, especially in response to rainfall and temperature.
Willingness and Perceived ability to pay for Uganda’s Proposed National Health Insurance Scheme among Informal Sector workers in Iganga and Mayuge districts, Uganda: A Contingent Valuation Method
Authors: Namuhani Noel , Kisakye Angela , Kiwanuka Suzanne N
Published: July 2024

Background

Access to health care remains a challenge, especially among the informal sector workers in most low-income countries, due to high out-of-pocket (OOP) expenditures, with Uganda spending over 28.0% out of pocket on health care. In response, Uganda has proposed a national health insurance scheme (NHI). However, the willingness and ability to pay for the proposed NHI scheme within the informal sector have not yet been explored in Uganda. This study assessed the willingness and perceived ability to pay for the proposed NHI scheme and its determinants among the informal sector workers in Iganga and Mayuge districts, Uganda.

Methodology

A cross-sectional study was conducted in Iganga and Mayuge districts in April and May 2019. A contingent valuation method using the bidding game technique was used to elicit the willingness to pay (WTP). A total of 853 informal sector workers, including farmers, commercial motorists, fishermen, and traders, were randomly sampled. Seven focus group discussions (FGD) were also conducted. Logistic regression was done to identify the determinants of willingness to pay for the proposed NHI scheme. Qualitative data was analyzed thematically.

Results

The majority 695/853, (81.5%) of the respondents were willing to pay for NHI; the median WTP was UGX 25,000 (USD 6.8) annually; and 633/853, (74.2%) of the respondents believed that they were able to pay for the health insurance. Willingness to Pay was significantly associated with being a fisher folk (AOR: 1.70 95%CI: 1.04-2.79, P = 0.035), being in the fourth wealth quintile (AOR: 2.98, 95% CI: 1.56–5.65), not hearing about health insurance (AOR: 0.50 95%CI: 0.23-0.86, P = 0.032), and not having saving group membership (AOR: 0.51, 95%CI: 0.34-0.76, P<0.001). Most of the FGD participants were willing to pay for the proposed scheme; however, some of the participants doubted their ability to pay for the scheme given their high poverty levels and their unstable income.

Conclusion

The willingness to pay for health insurance in the informal sector is high. Therefore, it is viable for the government to extend NHI to the informal sector. However, awareness building and due consideration of high poverty levels in setting appropriate premiums should be a priority.
Factors behind poor cognitive outcome following a thalamic stroke
Authors: Vidal Julie P. C. , Danet Lola , Arribarat Germain , Pariente Jérémie , Péran Patrice , Albucher Jean-François , Barbeau Emmanuel J.
Published: July 2024

Objective

Thalamic strokes produce a range of neurological, cognitive, and behavioral symptoms depending on the thalamic nuclei involved. While thalamic strokes are traditionally associated with severe cognitive deficits, recent studies suggest more modest impairments. This study aims to identify the factors that influence the severity of cognitive impairment following thalamic stroke.

Methods

We recruited 40 patients (median age 51) with chronic isolated thalamic stroke and 45 healthy subjects. All subjects underwent neuroimaging and neuropsychological testing. Cluster and principal component analyses were used to discriminate patients from healthy subjects based on cognitive performance. Disconnectome maps and cortical thickness were analyzed to understand the distant impact of thalamic strokes.

Results

Two cognitive profiles emerged. Cluster 1 included mostly healthy subjects (n = 43) and patients with no or minor deficits (n = 20); Cluster 2 included patients (n = 19) and 2 healthy subjects with severe deficits of verbal memory, executive functions, and attention. Cluster 1 included all patients with right thalamic stroke. Cluster 2 included all patients with bilateral stroke or mammillothalamic tract disruption. Patients with left-sided stroke were equally divided between Cluster 1 and 2. Other significant differences included age, education, interthalamic adhesion disruption, lesion volume, and location. Disconnectome maps showed larger disruptions of the anterior thalamic projection in patients with left-sided stroke of Cluster 2.

Interpretation

Contrary to common expectations, our findings indicate that many patients with thalamic stroke have relatively good cognitive outcomes. In contrast, we identified some of the factors behind poor outcomes that may help clinicians.
Second generation of LNP based mRNA vaccine leads to a T cell–inflamed tumor microenvironment favorable for improving PD-1/PD-L1 blocking therapy and long-term immunity in a cold tumor model
Authors: Fournier Carole , Mercey-Ressejac Marion , Derangère Valentin , Al Kadi Amal , Rageot David , Charrat Christine , Leroy Alexis , Escudé Marie , Escaich Séverine , Ghiringhelli François , Decaens Thomas , Navarro Fabrice P. , Jouvin-Marche Evelyne , Marche Patrice N.
Published: July 2024

The delivery of mRNA-based cancer vaccines has demonstrated significant promise in triggering antitumor immune responses. With the aim of using them in combination with other immunotherapies already used in the clinical appropriately, the modifications of the intratumoral immune microenvironment needs to be deeply characterized. We have shown that the second generation of lipid nanoparticles (LNPs), nanostructured lipid carriers (so-called Lipidots®), are able to vector protein antigens and nucleic acids. Here, we test Lipidots®for the delivery of mRNA encoding OVA antigen and eliciting a specific antitumor immune response. We demonstratein vitrothat our LNPs deliver mRNA into dendritic cells (DCs), when complexed with mRNA, activate DCs through the TLR4/8 and ROS signaling pathways and induce specific CD4+and CD8+T cell activation. Our vaccinal strategy exhibits significant antitumor efficacy both in the context of tumor prevention and as a therapeutic vaccine in B16OVA and E.G7-OVA cold tumors. The LNP-Ova mRNA vaccine induces a profound intratumoral remodeling of the innate and adaptive immunity associated with an increase in the gene expression of chemokines (Cxcl10, Cxcl11, Cxcl9) involved in CD8+T cell attraction. Additionally, the vaccine induces the establishment of an escape mechanism mediated by PD-1/PDL-1 axis, making it an adjuvant therapy for optimized responses to the blocking of this signaling pathway. Finally, the combination of vaccine and anti-PD-1 therapy achieves a much higher rate of complete responses and memory immune responses compared to monotherapies. Our work demonstrates the capability of Lipidots®as an effective platform for the development of preventive and therapeutic vaccines against cancer based on mRNA delivery and that combination with other immunotherapies such as immune checkpoint blockers could counter tumor resistance and promote long-term antitumor immunity.
Changes in maternal blood and placental lipidomic profile in obesity and gestational diabetes: Evidence for sexual dimorphism
Authors: Kadam Leena , Veličković Marija , Stratton Kelly , Nicora Carrie D. , Kyle Jennifer E. , Wang Eric , Monroe Matthew E. , Bramer Lisa M. , Myatt Leslie , Burnum-Johnson Kristin E.
Published: July 2024

Introduction

Obesity and gestational diabetes (GDM) are associated with adverse pregnancy outcomes and program the offspring for cardiometabolic disease in a sexually dimorphic manner. The placenta transfers lipids to the fetus and uses these substrates to support its own metabolism impacting the amount of substrate available to the growing fetus.

Methods

We collected maternal plasma and placental villous tissue following elective cesarean section at term from women who were lean (pre-pregnancy BMI 18.5-24.9), obese (BMI>30) and type A2 GDM (matched to obese BMI) with male or female fetus (n=4 each group). Lipids were extracted and fatty acid composition of different lipid classes were analyzed by LC-MS/MS analysis. Significant changes in GDM vs obese, GDM vs lean, and obese vs lean were determined using t-test with a Tukey correction set at p<0.05.

Results

In placental samples 436 lipids were identified, among which 85 showed significant changes. Of note only in male placentas significant decreases in C22:6 - docosahexaenoic acid (DHA) in phosphatidylcholine (PC) and triglyceride lipid species were seen when comparing tissue from GDM women to lean. In maternal plasma we observed no effect of obesity. GDM or fetal sex.

Conclusion

This is the first study assessing fatty acid composition of lipids in matched maternal plasma and placental tissue from lean, obese, and GDM women stratified by fetal sex. It highlights how GDM affects distribution of fatty acids in lipid classes changes in a sexually dimorphic manner in the placenta.
The Role of Artificial Intelligence in Modern Medical Education and Practice: A Systematic Literature Review
Authors: Rasouli Shiva , Alkurdi Duha , Jia Bochen
Published: July 2024

Abstract

The integration of Artificial Intelligence (AI) into medical education has emerged as a transformative element in the modern healthcare educational system. With the exponential growth of medical knowledge and the increasing complexity of healthcare systems, AI offers innovative solutions to enhance learning outcomes, facilitate personalized education pathways, and improve clinical decision-making skills among medical professionals. This literature review explores the transformative role of AI in the training of healthcare providers, focusing on advancements in medical education, medical diagnostics, and emergency care training. Additionally, it addresses the readiness of healthcare professionals to employ AI technologies, analyzing their current knowledge, attitudes, and the training provided. By synthesizing findings from multiple studies, we aim to highlight AI’s potential to enhance medical education, address challenges, and propose future directions for integrating AI into healthcare training.
Biom3d, a modular framework to host and develop 3D segmentation methods
Authors: Mougeot Guillaume , Safarbati Sami , Alégot Hervé , Pouchin Pierre , Field Nadine , Almagro Sébastien , Pery Émilie , Probst Aline , Tatout Christophe , Evans David E. , Graumann Katja , Chausse Frédéric , Desset Sophie
Published: July 2024

U-Net is a convolutional neural network model developed in 2015 and has proven to be one of the most inspiring deep-learning models for image segmentation. Numerous U-Net-based applications have since emerged, constituting a heterogeneous set of tools that illustrate the current reproducibility crisis in the deep-learning field and that remain slow to spread in application fields such as 3D bioimaging. Here we propose a solution named Biom3d, a modular deep learning framework facilitating the integration and development of novel models, metrics, or training schemes for 3D image segmentation. The development philosophy of Biom3d provides an improved code sustainability and reproducibility in line with the FAIR principles and is available as a graphical user interface and an open-source deep-learning framework to target a large community of users, from end users to deep learning developers.
Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway
Authors: Cantwell Helena , Nguyen Hieu , Kettenbach Arminja , Heald Rebecca
Published: July 2024

The transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug screening approach usingCionaeggs and found that inhibition of Casein Kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in cytoplasmic extracts prepared fromXenopuseggs. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences betweenXenopusmeiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors that induce mitotic spindle morphology.