bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel approach to distinguish complicated and non-complicated acute cholecystitis: Decision tree method
Authors: Gojayev Afig , Karakaya Emre , Erkent Murathan , Yücebaş Sait Can , Aydin Hüseyin Onur , Kavasoğlu Lara , Aydoğan Cem , Yildirim Sedat
Published: May 2023

It is difficult to differentiate between non-complicated acute cholecystitis (NCAC) and complicated acute cholecystitis (CAC) preoperatively, which are two separate pathologies with different management. The aim of this study was to create an algorithm that distinguishes between CAC and NCAC using the decision tree method, which includes simple examinations. In this retrospective study, the patients were divided into 2 groups: CAC (149 patients) and NCAC (885 patients). Parameters such as patient demographic data, American Society of Anesthesiologists (ASA) score, Tokyo grade, comorbidity findings, white blood cell (WBC) count, neutrophil/lymphocyte ratio, C-reactive protein (CRP) level, albumin level, CRP/albumin ratio (CAR), and gallbladder wall thickness (GBWT) were evaluated. In this algorithm, the CRP value became a very important parameter in the distinction between NCAC and CAC. Age was an important predictive factor in patients with CRP levels >57 mg/L, and the critical value for age was 42. After the age factor, the important parameters in the decision tree were WBC and GBWT. In patients with a CRP value of ≤57 mg/L, GBWT is decisive and the critical value is 4.85 mm. Age, neutrophil/lymphocyte ratio, and WBC count were among the other important factors after GBWT. Sex, ASA score, Tokyo grade, comorbidity, CAR, and albumin value did not have an effect on the distinction between NCAC and CAC. In statistical analysis, significant differences were found groups in terms of gender (34.8% vs 51.7% male), ASA score (P < .001), Tokyo grade (P < .001), comorbidity (P < .001), albumin (4 vs 3.4 g/dL), and CAR (2.4 vs 38.4). By means of this algorithm, which includes low-cost examinations, NCAC and CAC distinction can be made easily and quickly within limited possibilities. Preoperative prediction of pathologies that are difficult to manage, such as CAC, can minimize patient morbidity and mortality.
Implant selection in natural and stable direct-to-implant reconstruction with ten steps at nipple-sparing mastectomy
Authors: Sağir Mehmet , Güven Erdem , Eröz Seda , Uras Cihan
Published: May 2023

Direct-to-implant reconstruction is one of the breast repair techniques after mastectomy. Implant selection is critical in the short- and long-term success of direct-to-implant reconstruction after nipple-sparing mastectomy. In this study we developed a 10-step algorithm that we use before and during surgery. We aimed to obtain natural and stable breast reconstruction with this algorithm. In addition, we also aimed to evaluate which implants were selected using this algorithm and their short- and long-term outcomes. This retrospective study included 218 patients aged 27 to 60 years who underwent mastectomy and direct-to-implant reconstruction between November 2018 and December 2021. The patients were assigned into 4 groups according to amount of breast tissue removed. We developed a 10-step algorithm and these included: breast base, amount of breast tissue removed, evaluation of mastectomy skin flap, breast projection, ptosis, unilateral/bilateral reconstruction, chest wall deformity, patient’s request, comorbid conditions and stabilization and arrangement of novel sulcus. The evaluation was made when the patient’s photographs were taken at least 1 year after the surgery. The highest number of patients was recorded in group 3; in addition, mean age was also highest in group 3. The lowest number of patients was recorded in group 4. The body mass index showed a progressive increase from group 1 to group 4. Medium height moderate profile prosthesis was used in 81.7% while medium height moderate plus profile prosthesis was used in 18.3% of breasts included. We used larger prosthesis up to 58.1% when compared to the tissue removed in group 1 while we used smaller prosthesis by 25.6% in group 4. In the anterior view, the medial and lateral arch of the lower pole of the breast was obtained in all patients. Obvious asymmetry developed in 4 patients. In lateral and oblique views, upper and lower pole natural breast images were obtained in all patients, except for 5 patients. There was no sulcus inferior displacement in any patient. Implant extrusion did not occur in any patient. This algorithm is an easy to use and effective method to obtain a stable and natural breast image in the long-term.
Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database
Authors: Yacouba Mohamed Bassirou Moukeila , Feng Maohui , Thokerunga Erick , Bongolo Christian Cedric , Gado Adamou Foumakoye , He Feng , Ke Jianjuan , Zhang Zongze , Wang Yanlin
Published: May 2023

Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.
Long-term outcome of acute type A aortic dissection repair in chronic kidney disease patients
Authors: Chou An-Hsun , Hsieh Meng-Ling , Lin Yu-Sheng , Chen Dong-Yi , Chu Pao-Hsien , Chen Shao-Wei
Published: May 2023

Preoperative renal dysfunction is associated with mortality in patients with acute type A aortic dissection (ATAAD) repair. However, the long-term outcome of chronic kidney dysfunction (CKD) in ATAAD is unclear. The study aimed to evaluate the long-term outcome of CKD in patients with ATAAD repair. We retrospectively studied patients with ATAAD repair using data from the Taiwan’s National Health Insurance Research Database between July 1, 2004, and December 31, 2013. The outcomes of interest included all-cause mortality, readmission due to any cause, redo aortic surgery, major adverse cardiac and cerebrovascular events, and liver and renal outcomes. There were 3328 patients who received ATAAD repair. These patients were divided into CKD and non-CKD groups. In-hospital mortality in the CKD group was significantly higher than that in the non-CKD group (32.5% vs 18.8%, respectively, odds ratio 2.14, 95% confidence interval [CI] 1.37–3.36). During long-term follow-up, patients with CKD had higher risks of all-cause mortality including in-hospital death (52.6% vs 32.5%; hazard ratio 1.83, 95% CI 1.32–2.55), mortality after discharge (29.7% vs 16.8%; hazard ratio 2.09, 95% CI 1.02–4.29), and readmission rates (67.1% vs 51.6%; subdistribution hazard ratio 2.00, 95% CI 1.43–2.79). However, no significant difference was observed between the dialysis and non-dialysis groups. On the basis of our results, patients with CKD carry a poor long-term outcome after ATAAD repair. Cardiac surgeons should be aware of this condition when dealing with ATAAD repair.
Testosterone elevation in ovarian adult granulosa cell tumor: A case report and review of the literature
Authors: Jiang Ziwei , Qiu Yixuan , Hu Siwen , Li Yujing , Chen Xing , Jin Yichao , Dai Huihua
Published: May 2023

Rationale:

Adult granulosa cell tumors (AGCT) mainly secret estrogen, but few androgens. It is rarer to have amenorrhea and hyperandrogenemia as clinical features. Here, we report a rare case of right side AGCTs with amenorrhea and hyperandrogenemia in a 19-year-old female.

Patient concerns:

The 19-year-old patient was admitted to our hospital due to amenorrhea for more than 1 year, and discovery of pelvic mass for 4 months. The gynecological ultrasound and computed tomography (CT) cannot define the nature of the mass. Surprisingly, an elevation in testosterone levels was also measured.

Diagnosis and interventions:

The present patient underwent laparoscopic right salpingo-oophorectomy and partial omentectomy and biopsy of the peritoneum.

Outcomes:

After the surgery, the testosterone value was down to normal. The patient menstrual cramps on August 13, 2021. Her clitoris is smaller than the front. Up to August 1, 2022, there was no obvious sign of recurrence.

Lessons:

Androgen-secreting AGCT is rare. We hope that this case can strengthen gynecologists’ early diagnosis and treatment of this disease and improve the prognosis.
“The eyes are the windows of the soul”: Portable automated pupillometry to monitor autonomic nervous activity in CO2 narcosis: A case report
Authors: Yamaguchi Junko , Kinoshita Kosaku , Hosokawa Toru , Ihara Shingo
Published: May 2023

Rationale:

Altered autonomic responses can be observed in patients in the intensive care unit (ICU), and these changes in abnormal autonomic responses are known to be associated with patient prognosis. Therefore, it is important to monitor autonomic nervous system activity in these critically ill patients. While the utility of monitoring critically ill patients using heart rate (HR) variability measurements has been reported, portable automated pupillometers are small, lightweight, and easy-to-operate medical devices that may be more easily evaluated for autonomic nervous system function.

Patient concerns:

An unconscious 80-year-old female patient with chronic obstructive pulmonary disease was brought to the medical emergency department after a call from her caregiver.

Diagnosis:

On arrival, the patient’s Glasgow coma scale score was 7, her blood pressure was 140/80 mm Hg, her HR was 114 bpm, and her respiratory rate was 27 breaths/minutes with increased breathing effort. Oxygen saturation was 90% on a venturi mask (3 L of supplemental oxygen). The arterial blood gas analysis showed a pH of 7.196, a partial pressure of carbon dioxide (CO2) of 89.6 mm Hg, a partial pressure of oxygen of 87.5 mm Hg, and a bicarbonate level of 29.4 mmol/L. Other than CO2 narcosis, there were no abnormal findings to induce impaired consciousness. The patient did not respond to support with a bag-valve mask and was intubated. One hour after intubation, her impaired consciousness improved. The patient was extubated 20 hours later and discharged on Day 3.

Interventions:

The patient was admitted to the ICU after being intubated, where vital signs and blood gas analysis were monitored every 2 hours, and consciousness was assessed using the Glasgow coma scale. Using a portable automated pupillometer (NeurOptics NPi™-200, Neuroptics Inc., Irvine, CA), pupillary responses, including pupil size or light reflex, were measured every 2 hours during ICU stay.

Outcomes:

Changes in respiratory rate and partial pressure of CO2 values correlated with pupil size and constriction velocity, but HR changes were contrary.

Lessons:

Pupillary responses exhibited by automated pupillometers observed in patients with CO2 narcosis may be linked to vital signs and allow for autonomic evaluation.
Global research trends in prediction of difficult airways: A bibliometric and visualization study
Authors: Li Xiaoyan , Lian Yixiao , Pan Fang , Zhao Hong
Published: May 2023

Many tools are used to predict difficult airway, including bedside screening tests, radiological variables, and ultrasonography. However, the “gold standard” to identify difficult airway before intubation has not been established. The assessment and prediction of difficult airway is receiving increasing attention in clinical practice due to the devastating results of failed oxygenation or intubation. A literature visualization study is necessary to understand the research trend and help tailor future research directions. Science citation index-expanded web of Science database were used to search for literature related to assessment and prediction of difficult airways published before May 9th, 2022. VOS viewer software was used for visual analysis, including literature statistics, and co-occurrence analysis. A total of 2609 articles were included. The amount of relevant research interest and literature is increasing every year. According to co-occurrence network analysis, the research results can be grouped into the following 5 clusters, intubation approaches, intubation in special populations, difficult airway assessment tests, intubation in critical care/emergency settings and education, and laryngoscopes. Co-occurrence overlay analysis showed that video laryngoscopes and index prediction (including computed tomography and ultrasonography), emerged recently and comprised an important percentage of current studies. It can be predicted that future studies should focus on understanding the upper airway anatomy and constructing risk index predictions. Based on current global research trends, risk index predictions are the next hot topics in the evaluation and prediction of difficult airways, and video laryngoscopes will continue to be a hot topic in this field.
Lung abscess with chronic cough secondary to xanthogranulomatous pyelonephritis: A rare case report
Authors: Cheng Pai-Yu , Huang Yi-You , Jaw Fu-Shan , Chung Shiu-Dong
Published: May 2023

Rationale:

Xanthogranulomatous pyelonephritis (XGPN) is a form of chronic pyelonephritis caused by chronic calculus obstruction and bacterial infection, leading to the destruction of the renal parenchyma and calyces. Conservative treatment is usually not sufficient, and surgical intervention is still the main curative approach. XGPN with transdiaphragmatic extension and lung abscess formation is a rare condition.

Patient concerns:

We report a 64-year-old woman who presented with persistent productive cough.

Diagnoses:

Lung abscess secondary to XPGN. Both nephrostomy urine and sputum cultures showed Proteus mirabilis infection with the same antibiotic sensitivity spectrum, but blood culture was negative.

Interventions:

Laparoscopic radical nephrectomy and prolonged antibiotic treatment.

Outcomes:

The lung abscess and cough gradually resolved in 1 month after nephrectomy.

Conclusion:

Lung abscess secondary to transdiaphragmatic extension of XGPN is rare but should be considered in patients with lower lung infections that are unresponsive to treatment, especially infections due to unusual respiratory pathogens such as P mirabilis.
Tislelizumab for squamous lung cancer combined with basal cell carcinoma of the skin: A case report
Authors: Wu Ming-Jun , Chen Yu-Chun , Cui Xiao-Li , Yang Qian , Xue Qing-Liang
Published: May 2023

Introduction:

Surgery is the preferred treatment for basal cell carcinoma (BCC), locally advanced or metastatic BCC, radiation therapy or systemic therapy can be considered. Programmed death receptor 1 (PD-1) inhibitors are rarely used to treat cutaneous BCC. In the present case, we found that tislelizumab, a PD-1 immunosuppressant, had a positive effect on BCC.

Patient concerns:

A 74-year-old male patient presented with a mass in the left back in October 2021, which was surgically removed and diagnosed as BCC. The patient was diagnosed with squamous lung cancer after presenting with a cough and coughing up a small amount of white, sticky sputum in December 2021.

Diagnosis:

BCC and squamous lung cancer.

Interventions:

Docetaxel + nedaplatin systemic chemotherapy combined with tislelizumab immunotherapy.

Outcomes:

Both BCC and squamous lung cancer were significantly reduced in size.

Conclusion:

After 2 cycles of immunotherapy with tislelizumab, the lung tumor shrank, the back mass disappeared, and the wound healed.
Development of convolutional neural network model for diagnosing osteochondral lesions of the talus using anteroposterior ankle radiographs
Authors: Shin Hyunkwang , Park Donghwi , Kim Jeoung Kun , Choi Gyu Sang , Chang Min Cheol
Published: May 2023

Deep learning is an advanced machine learning technique that is used in several medical fields to diagnose diseases and predict therapeutic outcomes. In this study, using anteroposterior ankle radiographs, we developed a convolutional neural network (CNN) model to diagnose osteochondral lesions of the talus (OLTs) using ankle radiographs as input data. We evaluated whether a CNN model trained on anteroposterior ankle radiographs could help diagnose the presence of OLT. We retrospectively collected 379 cases (OLT cases = 133, non-OLT cases = 246) of anteroposterior ankle radiographs taken at a university hospital between January 2010 and December 2020. The OLT was diagnosed using ankle magnetic resonance images of each patient. Among the 379 cases, 70% of the included data were randomly selected as the training set, 10% as the validation set, and the remaining 20% were assigned to the test set to evaluate the model performance. To accurately classify OLT and non-OLT, we cropped the area of the ankle on anteroposterior ankle radiographs, resized the image to 224 × 224, and used it as the input data. We then used the Visual Geometry Group Network model to determine whether the input image was OLT or non-OLT. The performance of the CNN model for the area under the curve, accuracy, positive predictive value, and negative predictive value on the test data were 0.774 (95% confidence interval [CI], 0.673–0.875), 81.58% (95% CI, 0.729–0.903), 80.95% (95% CI, 0.773–0.846), and 81.82% (95% CI, 0.804–0.832), respectively. A CNN model trained on anteroposterior ankle radiographs achieved meaningful accuracy in diagnosing OLT and demonstrated that it could help diagnose OLT.
Oxidized LDL receptors: a recent update
Authors: Khan Mohd Azeem , Mohammad Irshad , Banerjee Sohom , Tomar Akanksha , Varughese Kottayil I , Mehta Jawahar L , Chandele Anmol , Arockiasamy Arulandu
Published: May 2023

Purpose of review

LDL in its oxidized form, or ‘oxLDL’, is now generally acknowledged to be highly proatherogenic and to play a significant role in atherosclerotic plaque formation. Therefore, there has been increasing interest in understanding the significance of oxLDL and its receptors in different phases of atherosclerosis, leading to the accumulation of additional data at the cellular, structural, and physiological levels. This review focuses on the most recent discoveries about these receptors and how they influence lipid absorption, metabolism, and inflammation in various cell types.

Recent findings

Two crystal structures of lectin-like oxLDL receptor-1 (LOX-1), one with a small molecule inhibitor and the other with a monoclonal antibody have been published. We recently demonstrated that the ‘surface site’ of LOX1, adjacent to the positively charged ‘basic spine region’ that facilitates oxLDL binding, is a targetable site for drug development. Further, recent human studies showed that soluble LOX-1 holds potential as a biomarker for cardiovascular disease diagnosis, prognosis, and assessing the efficacy of therapy.

Receptor-mediated oxLDL uptake results in cellular dysfunction of various cell types involved in atherogenesis and plaque development. The current advancements clearly demonstrate that targeting oxLDL-LOX-1 axis may lead to development of future therapeutics for the treatment of atherosclerotic cardiovascular and cerebrovascular diseases.
A novel tube for sperm density gradient centrifugation procedure
Authors: Xue Yun-Jing , Du Wei , Deng Cun-Zhong , Xu Yuan , Liu Chen-Chen , Yang Yan-Nan , Wang Ling , Lv Yu-Zhen , Li Zheng , Chian Ri-Cheng
Published: May 2023

Objective:

Density gradient centrifugation (DGC), swim up (SU), or a combination of DGC and SU is used to prepare sperm for infertility treatments using assisted reproductive technologies (ARTs). This study aimed to investigate the efficiency of a new device for detecting sperm DGC.

Methods:

Sperm samples were collected from 119 males who required semen analysis at three different in vitro fertilization (IVF) centers (71 samples from Center A, 28 samples from Center B, and 20 samples from Center C). Semen samples were divided into two groups for DGC: (1) a normal centrifugation tube and (2) a specially designed RC-Tube. The sperm concentration, motility, and DNA fragmentation index (DFI) were assessed using DGC. Sperm concentration and motility were assessed using a MAKLER counting chamber. Sperm DFI was measured and analyzed using flow cytometry using a DFI Kit.

Results:

There were no significant differences in sperm concentrations recovered following DGC between the two groups (31.1% ± 1.7% vs. 28.8% ± 1.3%). Sperm motility was not significantly different following the DGC procedure in both groups (77.6% ± 1.6%. vs. 75.8% ± 1.6%). The percentage of sperm DFI was also not significantly different following DGC between the two groups (10.4% ± 1.0% vs. 10.5% ± 1.0%).

Conclusions:

The newly designed RC-Tube is efficient for sperm DGC and can be used to simplify sperm preparation for infertility treatment.
A Novel Intraoperative Leak Test Procedure (GAM Procedure) to Prevent Postoperative Anastomotic Leakage in Gastric Cancer Patients Who Underwent Gastrectomy
Authors: Gao Zhenguo , Chen Xin , Bai Dan , Fahmy Lara , Qin Xiangzhi , Peng Yong , Ren Mingyang , Tian Yunhong , Hu Jiani
Published: May 2023

Background:

Anastomotic leakage following a radical gastrectomy is a serious complication of gastric cancer and esophagogastric junction cancer. The benefit of intraoperative leak testing for the prevention of postoperative anastomotic leakage has been controversial. We introduce a new procedure, which combines the techniques of gastroscopy, air, and methylene blue (GAM) for intraoperative leakage testing. Our objective was to evaluate the efficacy and safety of the GAM procedure for intraoperative leak testing and to compare the surgical complications of gastric cancer patients who underwent gastrectomy with and without intraoperative leak testing using the GAM procedure.

Materials and Methods:

A total of 210 patients who underwent radical gastrectomy for gastric cancer were included. Patients were divided into 2 groups: the intraoperative leak testing group using the GAM procedure (IOLT), and the group for which no intraoperative leak testing was done (NIOLT). Clinical and pathologic characteristics, the incidence of postoperative anastomotic leakage, and other surgical complications were compared between the 2 groups.

Results:

There were 82 patients in the IOLT group and 82 patients in the NIOLT group after propensity score matching. In the IOLT group, 4 (4.9%) patients were found to have anastomotic discontinuity during the operation; we repaired these anastomotic discontinuities intraoperatively. The incidence of postoperative anastomotic leakage was higher in the NIOLT group compared with the IOLT group, 6 (7.3%) versus 0 (0%), respectively (P=0.01). The average time of the GAM procedure was 4.99±1.75 minutes. The surgical time was prolonged by 30 minutes in the IOLT group compared with the NIOLT group, 302.2±79.9 versus 272.1±85.2, respectively (P=0.02). The length of hospital stay, 15.80±4.55 versus 17.00±6.20 (P=0.16) was reduced in the IOLT group compared with the NIOLT group. The logistic regression model suggested that IOLT, sex, age, Eastern Cooperative Oncology Group, cT stage, tumor diameter, pT stage, pN stage, and Lauren classification were not risk factors for postoperative complication.

Conclusions:

The GAM procedure of intraoperative leakage testing can effectively reduce the incidence of postoperative anastomotic leakage in gastric cancer patients undergoing gastrectomy.
Paenibacillus sedimenti sp. nov., isolated from freshwater wetland sediment
Authors: Yan Lei , Shi Jiajia , Cao Jiahui , Zhang Meng , Chen Linxia , Wang Lixin , Bao Zhihua
Published: May 2023

A Gram-stain-positive, motile, rod-shaped, facultatively anaerobic bacterium, designated strain WST5T, isolated from sediment was characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain WST5T was most closely related to

Paenibacillus aestuarii

CJ25T (96.8 % similarity). The genome size of the WST5T was 6.5 Mb, contained 4500 predicted protein-coding genes, and had a DNA G+C content of 46.6%. The values of whole-genome average nucleotide identity analysis and digital DNA–DNA hybridization between strain WST5T and its closely related type strains were less than 76 and 25.6 %, respectively. The predominant cellular fatty acids (>10 %) were anteiso-C15 : 0 and C16 : 1 ω5c and the main menaquinone was MK-7. The major polar lipids were identified as diphospholidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and two unknown aminophospholipids. Based on the results of phenotypic, genotypic, chemotaxonomic and phylogenetic analyses, strain WST5T is considered to represent a novel species of the genus

Paenibacillus

, for which the name Paenibacillus sedimentum sp. nov. is proposed. The type strain is WST5T (=NBRC 115194 T=CGMCC 1.18706T).
Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex
Authors: Hailu Elena , Cantillon Daire , Madrazo Carlos , Rose Graham , Wheeler Paul R. , Golby Paul , Adnew Bethlehem , Gagneux Sebastien , Aseffa Abraham , Gordon Stephen V. , Comas Iñaki , Young Douglas B. , Waddell Simon J. , Larrouy-Maumus Gerald , Berg Stefan
Published: May 2023

Lineage 7 (L7) emerged in the phylogeny of the

Mycobacterium tuberculosis

complex (MTBC) subsequent to the branching of ‘ancient’ lineage 1 and prior to the Eurasian dispersal of ‘modern’ lineages 2, 3 and 4. In contrast to the major MTBC lineages, the current epidemiology suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin. To search for microbiological factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages. The frequency of predicted functional mutations in L7 was similar to that documented in other lineages. These include mutations characteristic of modern lineages – such as constitutive expression of nitrate reductase – as well as mutations in the VirS locus that are commonly found in ancient lineages. We also identified and characterized multiple lineage-specific mutations in L7 in biosynthesis pathways of cell wall lipids, including confirmed deficiency of methoxy-mycolic acids due to a stop-gain mutation in the mmaA3 gene that encodes a methoxy-mycolic acid synthase. We show that the abolished biosynthesis of methoxy-mycolates of L7 alters the cell structure and colony morphology on selected growth media and impacts biofilm formation. The loss of these mycolic acid moieties may change the host–pathogen dynamic for L7 isolates, explaining the limited geographical distribution of L7 and contributing to further understanding the spread of MTBC lineages across the globe.
aaHash: recursive amino acid sequence hashing
Authors: Wong Johnathan , Kazemi Parham , Coombe Lauren , Warren René L. , Birol Inanç
Published: May 2023

Motivation

K-mer hashing is a common operation in many foundational bioinformatics problems. However, generic string hashing algorithms are not optimized for this application. Strings in bioinformatics use specific alphabets, a trait leveraged for nucleic acid sequences in earlier work. We note that amino acid sequences, with complexities and context that cannot be captured by generic hashing algorithms, can also benefit from a domain-specific hashing algorithm. Such a hashing algorithm can accelerate and improve the sensitivity of bioinformatics applications developed for protein sequences.

Results

Here, we present aaHash, a recursive hashing algorithm tailored for amino acid sequences. This algorithm utilizes multiple hash levels to represent biochemical similarities between amino acids. aaHash performs ∼10X faster than generic string hashing algorithms in hashing adjacentk-mers.

Availability and implementation

aaHash is available online athttps://github.com/bcgsc/btlliband is free for academic use.
Spontaneous Histone Exchange Between Nucleosomes
Authors: Das Subhra Kanti , Huynh Mai Thao , Lee Tae-Hee
Published: May 2023

The nucleosome is the fundamental gene-packing unit in eukaryotes. Nucleosomes comprise ∼147 bp DNA wrapped around an octameric histone protein core composed of two H2A-H2B dimers and one (H3-H4)2tetramer. The strong yet flexible DNA-histone interactions are a physical basis of the dynamic regulation of genes packaged in chromatin. The dynamic nature of DNA-histone interactions implies that nucleosomes dissociate DNA-histone contacts transiently and repeatedly. This kinetic instability may lead to spontaneous nucleosome disassembly or histone exchange between nucleosomes. At a high nucleosome concentration, nucleosome-nucleosome collisions and subsequent histone exchange would be a more likely pathway, where nucleosomes act as their own histone chaperone. The spontaneous histone exchange would serve as a mechanism for maintaining the overall chromatin stability although it has never been reported. We employed three-color single-molecule FRET (smFRET) to demonstrate that histone H2A-H2B dimers are exchanged spontaneously between nucleosomes and that the time scale is on a few tens of seconds at a physiological nucleosome concentration. The rate of histone exchange increases at a higher monovalent salt concentration, with histone acetylated nucleosomes, and in the presence of histone chaperone Nap1, while it remains unchanged at a higher temperature, and decreases upon DNA methylation. These results support histone exchange via transient and repetitive partial disassembly of the nucleosome and corroborate spontaneous histone diffusion in a compact chromatin context, modulating the local concentrations of histone modifications and variants.
Diversity of mycotoxins and other secondary metabolites recovered from blood oranges infected byColletotrichum,Alternaria, andPenicilliumspecies
Authors: Rovetto Ermes Ivan , Luz Carlos , La Spada Federico , Meca Giuseppe , Riolo Mario , Cacciola Santa Olga
Published: May 2023

This study identified secondary metabolites produced byAlternaria alternata,Colletotrichum gloeosporioidesandPenicillium digitatumin fruits of two blood orange cultivars before harvest. Analysis was performed by UHPLC–Q-TOF-MS. Three types of fruits were selected, asymptomatic, symptomatic showing necrotic lesions caused by hail, and mummified. Extracts from peel and juice were analyzed separately.Penicillium digitatumwas the prevalent species recovered from mummified and hail-injured fruits. Among 47 secondary metabolites identified, 16, 18 and 13 were ofA. alternata,C. gloeosporioidesandP. digitatum, respectively. Consistently with isolations, indicating the presence of these fungi also in asymptomatic fruits, the metabolic profiles of the peel of hail-injured and asymptomatic fruits did not differ substantially. Major differences were found in the profiles of juice from hail injured and mummified fruits, such as a significant higher presence of 5,4-dihydroxy-3,7,8-trimethoxy-6C-methylflavone and Atrovenetins, particularly in the juice of mummified fruits of Tarocco Lempso cultivar. Moreover, the mycotoxins Patulin and Rubratoxin B were detected exclusively in mummified fruits. Patulin was detected in both the juice and peel, with a higher relative abundance in the juice, while Rubratoxin B was detected only in the juice. These findings provide basic information for evaluating and preventing the risk of contamination by mycotoxins in the citrus fresh fruit supply chain and juice industry.
Sequence-Dependent Material Properties of Biomolecular Condensates and their Relation to Dilute Phase Conformations
Authors: Devarajan Dinesh Sundaravadivelu , Wang Jiahui , Szała-Mendyk Beata , Rekhi Shiv , Nikoubashman Arash , Kim Young C. , Mittal Jeetain
Published: May 2023

Material properties of phase-separated biomolecular assemblies, enriched with disordered proteins, dictate their ability to participate in many cellular functions. Despite the significant effort dedicated to understanding how the sequence of the disordered protein drives its phase separation to form condensates, little is known about the sequence determinants of condensate material properties. Here, we computationally decipher these relationships for charged disordered proteins using model sequences comprised of glutamic acid and lysine residues as well as naturally occurring sequences of LAF1’s RGG domain and DDX4’s N-terminal domain. We do so by delineating how the arrangement of oppositely charged residues within these sequences influences the dynamical, rheological, and interfacial properties of the condensed phase through equilibrium and non-equilibrium molecular simulations using the hydropathy scale and Martini models. Our computations yield material properties that are quantitatively comparable with experimentally characterized condensate systems. Interestingly, we find that the material properties of both the model and natural proteins respond similarly to the segregation of charges, despite their very different sequence compositions. Condensates of the highly charge-segregated sequences exhibit slower dynamics than the uniformly charge-patterned sequences, because of their comparatively long-lived molecular contacts between oppositely charged residues. Surprisingly, the molecular interactions within the condensate are highly similar to those within a single-chain for all sequences. Consequently, the condensate material properties of charged disordered proteins are strongly correlated with their dense phase contact dynamics and their single-chain structural properties. Our findings demonstrate the potential to harness the sequence characteristics of disordered proteins for predicting and engineering the material properties of functional condensates, with insights from the dilute phase properties.
Elevated prevalence and treatment of sleep disorders from 2011 to 2020; a nationwide population-based retrospective cohort study in Korea
Authors: Ahn Eun Kyoung , Baek Younghwa , Park Ji-Eun , Lee Siwoo , Jin Hee-Jeong
Published: May 2023

Objectives

This study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last ten years.

Methods

This is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses, and prescribed amounts for sleep disorders were recorded.

Results

The prevalence of sleep disorders increased from 3,867,975 (7.62%) in 2011 to 7,446,846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9,011,692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine.

Conclusions

Sleep disorders are continuously increasing, as is the use of medical services – personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognized as a significant health problem that needs to be actively addressed to improve quality of life.

Strengths and limitations of this study

This is a nationwide health insurance claims data for prevalence and the status of treatment on sleep disorders for ten years.

This study will be meaningful because we have confirmed the current address of the prevalence and treatment of sleep disorders in the last 10 years.

The data source has the limitation of being able to confirm only the items subject to health insurance benefits and review.

The results of tests for the diagnosis of sleep disorders were not confirmed.
Respiratory Complex I Regulates Dendritic Cell Maturation in Explant Model of Human Tumor Immune Microenvironment
Authors: Turpin Rita , Liu Ruixian , Munne Pauliina M. , Peura Aino , Rannikko Jenna H. , Philips Gino , Boeckx Bram , Salmelin Natasha , Hurskainen Elina , Suleymanova Ilida , Vuorinen Elisa M. , Lehtinen Laura , Mutka Minna , Kovanen Panu E. , Niinikoski Laura , Meretoja Tuomo , Mattson Johanna , Mustjoki Satu , Saavalainen Päivi , Goga Andrei , Lambrechts Diether , Pouwels Jeroen , Hollmén Maija , Klefström Juha
Published: May 2023

Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. Here we establish a Patient-Derived Explant Culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+ T cell cytotoxic activity. We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax + metformin drug combinationex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+ T cells and thus facilitating anti-tumor immunity. Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.
Schistosoma haematobiumandSchistosoma bovisfirst generation hybrids undergo large gene expressions remodeling consistent with species compatibility
Authors: Mathieu-Bégné Eglantine , Kincaid-Smith Julien , Chaparro Cristian , Allienne Jean-François , Rey Olivier , Boissier Jérôme , Toulza Eve
Published: May 2023

When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To the date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap especially in non-model organisms. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrid between the blood fluke parasitesS. haematobiumandS. bovis. To this aim we fist assembled a hybrid reference transcriptome allowing us to measure gene expression in both parental species and hybrids to further described and quantified the profiles of gene expression encountered in hybrids. We identified large-scale gene expression remodeling since up to 55% of genes were differentially expressed in hybrids compared to at least one of the parental species. We further showed that intermediate level of expression in hybrids compared to parental species was the most prevalent expression profile (38% of genes) in agreement withS. haematobium x S. bovishigh genomic compatibility and limited divergence. Also, among the differentially expressed genes of each of the identified profiles (intermediate, under-, over-expressed, or matching the expression of one of the parental species), only a few biological processes were found enriched without patterns being consistent through crosses and sexes. Our findings suggest that hybrid heterosis could be due to change in expression of a large portion of random genes which affect various biological processes.

Author Summary

When two species manage to produce a viable offspring, due to different parental genetic material, new allelic interactions might arise. We do not know much about how genes are expressed in such hybrids compared to their parental species and especially for non-model species. Here we gene expressions in first generation hybrids of two blood flukes’ parasitesSchistosoma haematobiumandS. bovis.We quantified and categorized gene differentially expressed in first generation hybrids. We showed that more than half the genes of the hybrids were differentially expressed compared to at least one of their parental species, hence showing major gene expression remodeling occurring during hybridization. However, the most common hybrid expression pattern was intermediate level of expression compared to parental species and various but no specific biological processes were associated with hybrids differentially expressed genes. We hypothesized that becauseS. haematobiumandS. bovisremain very compatible, when hybridizing many non-specific genes can have their expression level remodeled hence impacting the overall molecular machinery of the offspring while still sustaining highly operational hybrids.
The Upstream Sequence Transcription Complex Dictates Nucleosome Positioning and Promoter Accessibility at piRNA Genes in theC. elegansGerm Line
Authors: Sanchez Nancy , Gonzalez Lauren E , Reinke Valerie
Published: May 2023

The piRNA pathway is a conserved germline-specific small RNA pathway that ensures genomic integrity and continued fertility. InC. elegansand other nematodes, Type-I piRNA precursor transcripts are expressed from over 10,000 small, independently regulated genes clustered within two discrete domains of 1.5 and 3.5 MB on Chromosome IV. These large clusters likely play a significant role in promoting germline-specific expression of piRNAs, but the underlying mechanisms are unclear. By examining the chromatin environment specifically in isolated germ nuclei, we demonstrate that piRNA clusters are located in closed chromatin, and confirm the enrichment for the inactive histone modification H3K27me3. We further show that the piRNA biogenesis factor USTC (Upstream Sequence Transcription Complex) plays two roles – it promotes a strong association of nucleosomes throughout the piRNA clusters, and it organizes the local nucleosome environment to direct the exposure of individual piRNA genes. Overall, this work reveals new insight into how chromatin state coordinates transcriptional regulation over large genomic domains, which has implications for understanding global genome organization in the germ line.
RBM3 enhances cold resistance by regulating thermogenic gene expressions
Authors: Nakamura Junnosuke , Uno Megumi , Taketomi Takumi , Yadav Manoj Kumar , Tsuruta Fuminori
Published: May 2023

Mammals are thermostatic animals capable of regulating their body temperature within a precise range, irrespective of ambient temperature conditions. However, the precise mechanisms by which a body temperature is controlled dependent on ambient temperature are still unclear. Here, we report that RNA binding motif protein 3 (RBM3), one of the cold-responsive proteins, regulates body temperature via expressing thermogenic genes during the late-postnatal period. The body temperature inRbm3knockout (KO) juvenile mice was unstable and increased vulnerability to cold exposure. In addition,Rbm3KO mice exhibited increased lipid droplets in brown adipose tissue (BAT) and abnormal histology. The single-cell RNA-seq (scRNA-seq) analysis revealed that RBM3 is highly expressed in proliferating and differentiating cells in BAT. Moreover, RBM3 was necessary for upregulating thermogenic genes after cold shock. Notably, RBM3 interacted with UCP1 mRNAin vivo, thereby stabilizing its mRNA levels. Lastly, RBM3 regulated neuronal activity in the dorsomedial hypothalamic nucleus (DMH) under a cold environment. These data suggest that RBM3 regulates thermogenesis in juvenile mice through both upregulating thermogenic genes in BAT and activating DMH neurons after cold exposure.
Spatial biology of Ising-like synthetic genetic networks
Authors: Simpson Kevin , L’Homme Alfredo , Keymer Juan , Federici Fernán
Published: May 2023

Background

Understanding how spatial patterns of gene expression emerge from the interaction of individual gene networks is a fundamental challenge in biology. Developing a synthetic experimental system with a common theoretical framework that captures the emergence of short- and long-range spatial correlations (and anti-correlations) from interacting gene networks could serve to uncover generic scaling properties of these ubiquitous phenomena.

Results

Here, we combine synthetic biology, statistical mechanics models and computational simulations to study the spatial behavior of synthetic gene networks (SGNs) inEscherichia coliquasi-2D colonies growing on hard agar. Guided by the combined mechanisms of the contact process lattice simulation and two-dimensional Ising model (CPIM), we describe the spatial behavior of bi-stable and chemically-coupled SGNs that self-organize into patterns of long-range correlations with power-law scaling or short-range anti-correlations. These patterns, resembling ferromagnetic and anti-ferromagnetic configurations of the Ising model near critical points, maintain their scaling properties upon changes in growth rate and cell shape.

Conclusions

Our findings shed light on the spatial biology of coupled and bistable gene networks in growing cell populations. This emergent spatial behavior could provide insights into the study and engineering of self-organizing gene patterns in eukaryotic tissues and bacterial consortia.