bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic effect of low frequency electric pulse therapy on cisplatin-based chemotherapy-induced nausea and vomiting in patients with lung adenocarcinoma: A prospective controlled study
Authors: Hu Ming , Yao Lanhui , Li Li , Han Yonghong , Wang Yuanyuan , Lei Zhang , Wu Hongbin
Published: August 2022

To explore the efficacy of low-frequency electric pulse therapy (LFEPT) combined with 2 antiemetics in the prevention and treatment of cisplatin-based chemotherapy-induced nausea and vomiting (CINV) in patients with lung adenocarcinoma. A total of 82 patients with lung adenocarcinoma who received cisplatin-based chemotherapy were randomly divided into the experimental group (n=41) and control group (n=41) by random numerical table method. The experimental group was treated with LFEPT combined with 2 antiemetic drugs (tropisetron hydrochloride and dexamethasone hydrochloride), while the control group was treated with the same 2 antiemetic drugs. Revised index of nausea and vomiting and retching (R-INVR) and Functional Living Index-Emesis (FLIE) scale were used to quantitatively evaluate the symptoms of nausea and vomiting after chemotherapy, and the effect of LFEPT in the prevention and treatment of CINV was observed. The baseline characteristics had no statistical difference between the 2 groups. The degree of nausea reaction, vomiting, and dry retching were similar in 2 groups on the first day after chemotherapy. However, the degree of nausea reaction, vomiting, and dry retching were significantly improved in the experimental group than that of the control group on 2 to 5 days with all P<.05. The score of FLIE had no difference between the 2 groups on the first day after chemotherapy (84.05 vs 82.69, P=.30), and the score was significantly higher in experiment group on day 6 compared with the control group (103.71 vs 89.38, P=.02). The side effects had no difference between the 2 groups. The LFEPT can significantly ameliorate CINV in patients with lung adenocarcinoma, which is worthy of clinical application.
Investigation of typhlitis in bone marrow transplant patients in a stem cell transplant unit
Authors: Deveci Burak , Kublashvili George , Yilmaz Saim , Özcan Bariş , Korkmaz Halil Fatih , Gürsoy Olcay , Toptaş Tayfur , Döşemeci Levent , Saba Rabin
Published: August 2022

Typhlitis is a special type of enterocolitis that specifically develops in immunosuppressive patients with hematological malignancies. Typhlitis is a common consideration after bone marrow transplantation due to high-dose chemotherapy that is used in conditioning regimens those contain high-dose cytotoxic chemotherapeutic agents. Although there are several studies about typhlitis during chemotherapy or in leukemia patients, there is not enough data evaluating its relationship between stem cell transplant in adults. Therefore, the current study aimed to analyze the possible causes that may lead to the development of typhlitis in hematopoietic stem cell recipient patients. This retrospective study included 210 adult patients who underwent bone marrow transplantation between January 2017 and December 2019. Pediatric patients (patients younger than 18 years of age) were excluded. Patients’ data were evaluated to determine their effects on typhlitis and the mortality risk of the patients with typhlitis. The analysis of the variables was performed using the IBM SPSS Statistics for Windows version 26 (IBM Corp., Armonk, NY).Variables were analyzed at a 95% confidence level and a P value <0.05 was considered significant. Typhlitis developed in 23 (10.9%) transplant patients. Male sex, length of hospital stay, presence of febrile neutropenia, antibiotic and antifungal use, need for switching antibiotics, duration of neutropenia, diarrhea and antibiotic use in days were risk factors for development of typhlitis. It was observed that 100-days mortality was higher in typhlitis group reaching to a statistical significance (P < .05). In multiple logistic regression analysis, presence of mucositis and additional source of infection were determined as independent risk factors for the development of typhlitis in bone marrow transplant patients. This study provides valuable information for bone marrow transplant patients through an analysis of risk factors for the development of typhlitis. According to our results, mucositis and additional bacterial infections were found as risk factors for typhlitis therefore it would be beneficial for clinicians to consider these factors in patient follow-up. However, due to the retrospective nature of our study, prospective studies are needed to investigate risk factors and optimum treatment methods for typhlitis.
Efficacy and safety of optional parenteral antimicrobial therapy for complicated skin and soft tissue infections: A systematic review and Bayesian network meta-analysis
Authors: Li Huijuan , Liang Xueyan , Mo Guangyan , Guo Sitong , Chen Xiaoyu , Li Yan
Published: August 2022

Background:

Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus. This study aims to investigate the efficacy and safety of optional antimicrobial therapy for the treatment of complicated SSTIs (cSSTIs).

Methods:

We searched PubMed, Medline (Via Ovid SP), Embase (Via Ovid SP), and the Cochrane Central Register of Controlled Trials from their inception to March 22, 2021 for randomized controlled trials (RCTs) that studied the use of optional antimicrobial therapy for cSSTIs. Citations’ screening, study selection, data extraction, and risk of bias assessment were independently performed by 2 authors. The primary outcomes were clinical and microbiological treatment success, and adverse events (AEs) were also assessed.

Results:

A total of 48 trials covering 24,381 patients assessing 20 types of antimicrobial treatment modalities were included. Overall, omadacycline was associated with the highest beneficial effect on clinical and microbiological treatment success and with the largest rank probability based on surface under the cumulative ranking curve values, avarofloxacin was closely followed. Both had, however, omadacycline was related to moderately safety profiles. Lefamulin ranked as the best option was associated with the lowest risk of severe AEs. Subgroup analysis showed similar results. The quality of primary outcomes was moderate to low.

Conclusions:

The use of omadacycline was associated with higher rates of clinical and microbiological treatment success for the treatment of cSSTIs, with a relative low risk of AEs. Due to the limitations of the included RCTs, high-quality and well-designed RCTs are needed to further confirm the results.
The expression of POSTN and immune cell infiltration are prognostic factors of lung adenocarcinoma
Authors: Gao Fang , Liu Jin , Gan Hua
Published: August 2022

The objective of this study is to identify useful prognostic factors of lung adenocarcinoma (LUAD) by evaluating the changes of periostin (POSTN) expression activity and immune cell infiltration using public data repositories. The gene and protein expressions of POSTN in LUAD were collected and analyzed from Ualcan and Human Protein Atlas online database. The cell infiltration data of immune cells in LUAD patients were retrieved and processed using the TIMER tool. Cox regression analysis was employed to screen and characterize prognosis factors, Kaplan–Meier Plotter was used to analyze the survival curve of LUAD patients, and receiver operating characteristic curve was used to calculate the relationship between temporal POSTN expressions and the prognosis of LUAD. The expression activity of POSTN in LUAD was higher than that in normal tissues. With the exception of B cell which showed opposite correlationship, the infiltration of most immune cells, namely CD8+ T cells, macrophages, neutrophils, and dendritic cells, was positively correlated with the POSTN expression activity. Together, our investigation suggested that the POSTN expression activity and B-cell infiltration were the prognostic factors of LUAD. In addition, the 1-year negative predictive value of the POSTN expression activity for overall survival, disease-free survival, and progression-free interval was 0.902, 0.926, and 0.838, respectively. Along with decreased B-cell infiltration, the elevated expression of POSTN is an important factor of LUAD prognosis.
Correlations of ALD, Keap-1, and FoxO4 expression with traditional tumor markers and clinicopathological characteristics in colorectal carcinoma
Authors: Huang Pan , Wang Siyu , Wu Zhipeng , Zhou Zhengrong , Kuang Meiqian , Ren Caifang , Qian Xin , Jiang Anqi , Zhou Yan , Wang Xuxin , Shao Genbao
Published: August 2022

Aldolase A (A-2) (ALD), Kelch-like-ECH associated protein-1 (Keap-1), and Forkhead box O4 (FoxO4) are key regulatory proteins, which have been proven to be involved in tumor development. However, the clinicopathological significance of ALD, Keap-1, and FoxO4 expressions in colorectal (colon) carcinoma (CRC) is not clearly known. We sought to explore the clinicopathological significance of ALD, Keap-1, and FoxO4 in CRC to provide evidences for potential monitoring index of CRC. Cases of 199 CRC patients were analyzed retrospectively. Evaluation of ALD, cAMP response element-binding protein-2, cyclo-oxygenase 2, FoxO4, Keap-1, and p53 expressions in CRC patients was accomplished with immunohistochemical technique. The patients were divided into negative and positive groups in accordance with immunohistochemical result. We compared the clinicopathological characteristics of the patients in the 2 groups, coupled with analysis of the relationship between 6 aforesaid proteins and clinicopathological characteristics. Herein, we confirmed the association of tumor location with the expression of ALD, Keap-1, and FoxO4. Also, tumor differentiation was observed to associate significantly with the expression of Keap-1, FoxO4, and Cox-2. The data also revealed that there was a correlation between smoking and expression of ALD, Keap-1, FoxO4, p53, and Cox-2. Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC.
Effects of Phellinus linteus extract on immunity improvement: A CONSORT-randomized, double-blinded, placebo-controlled trial
Authors: Ku Yong Ho , Kang Jae Hui , Lee Hyun
Published: August 2022

Background:

Immunity protects the body from external threats and prevents the development of cancer. Biological response modifiers extracted from natural sources are being actively studied, and the immunostimulatory and anticancer effects of various types of fungi have been reported. However, there are no previous clinical studies on the immune-enhancing effect of Phellinus linteus (PL). Lactate dehydrogenase cytotoxicity assay is a prerequisite in order to get approval for using PL as a raw material in functional supplements and medicines in Korea. However, due to the absence of precedent clinical trials, the use of PL in supplements has been hindered. but there is no precedent clinical trial using it. We conducted a randomized, double-blinded, placebo-controlled trial to confirm the efficacy and safety of PL extract for the improvement of immunity using the lactate dehydrogenase cytotoxicity assay.

Methods:

A total of 98 subjects were enrolled and randomly assigned to 2 groups. Subjects in the PL and placebo groups received 1000 mg of PL extract and 1000 mg of dextrin per day, respectively (one capsule, twice every day for 8 weeks). The primary outcome measured was the activity of natural killer cells. Secondary outcomes were the levels of TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12, IgG1, IgG2, and IgM. Safety was evaluated using laboratory tests.

Results:

NK cell activity was significantly increased in the PL group compared to the placebo group (P < .05). Despite the absence of significant changes in secondary outcomes, there was a tendency for improvement in the PL group. PL extract-related adverse outcomes, particularly in liver and renal function, were not observed.

Conclusion:

PL extract may improve immunity and is safe to be consumed orally.
Using neutrophil to lymphocyte ratio to predict discharge among geriatric patients with influenza infection in emergency department
Authors: Jheng Jing-Cheng , Tseng Yen-Ting , Wang Te-Hao , Chen Li-Fu , Chung Jui-Yuan
Published: August 2022

The neutrophil-to-lymphocyte ratio (NLR) is used to predict the prognosis of various diseases, such as coronavirus disease 2019, community-acquired pneumonia, bacteremia, and endocarditis. However, NLR has never been reported to predict patient discharge in geriatric patients with influenza infection. This retrospective case-control study enrolled geriatric patients (≥65 years) with influenza virus infection who visited the emergency department of a medical center between January 01, 2010 and December 31, 2015. Demographic data, vital signs, past histories, influenza subtypes, outcomes, and disposition were analyzed. The optimal NLR cut-off value to predict patient discharge was determined using the Youden index. We also evaluated the accuracy of NLR in predicting patient discharge using logistic regression and receiver operating characteristic analysis. The study included 409 geriatric patients in the emergency department with a mean age of 79.5 years and an approximately equal sex ratio. NLR was significantly lower in the discharged group than in the nondischarged group (5.8 ± 3.7 vs 9.7 ± 8.4). Logistic regression revealed that patients with NLR ≤ 6.5 predicted discharge with an odds ratio of 3.62. The Hosmer–Lemeshow goodness-of-fit test was calculated as 0.36, and the adjusted area under the receiver operating characteristic was 0.75. The negative predictive value of NLR ≤ 6.5, to predict patient discharge, was 91.8%. NLR ≤ 6.5 is a simple and easy-to-obtain laboratory tool to guide the physicians to discharge geriatric patients with influenza infection in the crowded emergency department.
The association between vitamin D levels and heart rate variability in patients with type 2 diabetes mellitus
Authors: Chen Li Ye , Ye Xin Hua , Cheng Jin Luo , Xue Yun , Li De , Shao Jie
Published: August 2022

To assess the association between serum vitamin D levels and heart rate variability in patients with type 2 diabetes mellitus (T2DM). This study included 469 patients who were retrospective assessed for eligibility from Changzhou Second People’s Hospital, Affiliated Nanjing Medical University, between March 2013 and June 2020. A total of 191 T2DM patients were recruited and divided into 3 groups. A total of 191 patients were recruited. A significant difference was noted among groups for HbA1c (P < .001), serum uric acid (P = .048), and urea nitrogen (P = .043). The Vitamin D level in deficiency, insufficiency, and sufficient was 23.17, 38.89, and 63.01 nmol/L, respectively. The insufficient group had lower levels of percentage of normal-to-normal intervals differing by more than 50 milliseconds, and the square root of the mean of the squares of the differences between adjacent normal-to-normal R peak-to-R-peak time intervals than the sufficient vitamin D group. Furthermore, patients in deficiency and insufficiency group were associated with high level of low frequency power/high frequency power as compared with sufficient vitamin D group. Finally, serum 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with rMSSD (P = .002). This study found that low serum 25(OH)D levels were associated with reduced heart rate variability parameters in patients with T2DM.
Diffused bladder wall calcification in a survivor with severe coronavirus disease 2019: A case report
Authors: Cheng Pai-Yu , Huang Yi-You , Jaw Fu-Shan , Chung Shiu-Dong , Tsai Chung-You
Published: August 2022

Rationale:

Bladder calcification is a rare presentation that was first interpreted to be related to a urea-splitting bacterial infection. Aside from infection, other hypotheses such as schistosomiasis, tuberculosis, cancer, and cytokine-induced inflammatory processes have also been reported. Severe coronavirus disease 2019 (COVID-19) is known for its provoking cytokine storm and uninhibited systematic inflammation, and calcification over the coronary artery or lung has been reported as a long-term complication.

Patient concerns:

We presented a 68 years old man who had persistent lower urinary tract symptoms after recovery from severe COVID-19. No urea-splitting bacteria were identified from urine culture.

Diagnosis:

Cystoscopy examination revealed diffuse bladder mucosal and submucosa calcification.

Interventions:

Transurethral removal of the mucosal calcification with lithotripsy.

Outcomes:

The patient’s lower urinary tract symptoms improved, and stone analysis showed 98% calcium phosphate and 2% calcium oxalate. No newly formed calcifications were found at serial follow-up.

Conclusion:

Diffuse bladder calcification may be a urinary tract sequela of COVID-19 infection. Patients with de novo lower urinary tract symptoms after severe COVID-19 should be further investigated.
Comparison of antimicrobial resistance in patients with obstructive pyelonephritis associated with ureteral stones and uncomplicated pyelonephritis
Authors: Jang Young Rock , Won Jeongyeon , Han Jung , Chung Wookyung , Ahn Su Joa
Published: August 2022

This study aimed to investigate the clinical outcomes of causative microorganisms in obstructive pyelonephritis associated with ureteral stones (OPU) and their antibiotic susceptibilities. This retrospective cohort study included female patients diagnosed with community-acquired acute pyelonephritis (APN) at a tertiary-care hospital between 2008 and 2017. A comparison of APN cases associated with the obstruction of the upper urinary tract by ureteral stones and APN cases without complications was performed. Propensity score (PS) matching was used to adjust the heterogeneity within each group. Of the 588 female patients with community-acquired APN, 107 were diagnosed with OPU and 481 with uncomplicated APN. After PS matching, Enterobacteriaceae strains isolated from OPU cases were more resistant to fluoroquinolones (51.9% vs 16.0%, P < .001). Extended-spectrum β-lactamase was detected in 22.2% and 21.0% of the Enterobacteriaceae strains isolated from OPU and uncomplicated APN cases, respectively (P = 1.000). The treatment failure rate was similar in OPU and uncomplicated APN groups (16.0% vs 21.0%, P = .545). Patients with OPU may be empirically treated with antibiotics in accordance with the treatment protocol for general pyelonephritis. Clinicians should exercise caution in prescribing fluoroquinolones for treating OPU.
Efficacy and long-term results of endovascular embolization and surgical clipping for posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy
Authors: Shen Xun , Wang Wenlei , Qin Huaihai , Ren Chun-Feng , Gao Bu-Lang
Published: August 2022

This study aimed

to investigate the efficacy and long-term outcomes of endovascular embolization and surgical clipping for patients with posterior communicating artery unruptured aneurysms (PcomAs) concomitant with oculomotor nerve palsy (ONP). No significant (P > .05) difference existed in the age, gender, proportion of complete ONP, and size of eye fissure and pupil before treatment between 2 groups. After compared with before treatment, the eye fissure was widened significantly (P < .05) and the pupil narrowed significantly (P < .05), but no significant (P > .05) differences existed between the 2 groups. Complete ONP recovery was observed in 32 (80%) patients in the embolization group and 31 (77.5%) in the microsurgical group, partial ONP recovery occurred in 6 (15%) in the embolization group and 8 (20%) in the microsurgical group. The recovery rate was 95% in the embolization group and 97.5% in the microsurgical group, with no significant (P > .05) difference between 2 groups. The recovery rate of the ONP was significantly (P < .01) greater in the microsurgical group than that in the embolization group at follow-up of 1 month, 3 months, six and 12 months, respectively. At 18 months, the ONP recovery rate was not significantly different between 2 groups (95% vs 97.5%) Surgical clipping may have a faster effect on the recovery of oculomotor nerve palsy than endovascular embolization for patients with posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy, but both approaches may result in a similar effect on the nerve recovery in the long run.

Eighty patients treated with endovascular embolization or surgical clipping were retrospectively enrolled into the endovascular embolization group or surgical clipping and analyzed.
Clinicopathologic and Prognostic Features of Pediatric Follicular Cell–derived Thyroid Carcinomas
Authors: Saliba Maelle , Alzumaili Bayan A. , Katabi Nora , Dogan Snjezana , Tuttle Robert M. , Zoltan Antal , Pandit-Taskar Neeta , Xu Bin , Ghossein Ronald A.
Published: August 2022

Pediatric thyroid carcinomas (TCs) are rare and mainly approached based on data extrapolated from adults. We retrospectively reviewed 222 pediatric TCs (patient age less than or equal to 21 y). Lymph node (LN) disease volume at presentation was considered high if the largest positive LN measured ≥1 cm and/or >5 LNs were positive. High-grade follicular cell–derived thyroid carcinoma (HGFCTC) were defined by the presence of marked mitotic count and/or tumor necrosis and considered as high-risk histology along with papillary thyroid carcinomas (PTC) diffuse sclerosing variant (DSV). Disease-free survival (DFS) was analyzed. LN involvement at presentation was significantly associated with male sex, larger tumor size, lymphatic invasion, positive surgical margins, and distant metastases at presentation. Five- and 10-year DFS was 84% and 77%, respectively. Only 1 patient with HGFCTC died of disease. Within PTC variants, PTC-DSV was associated with adverse histopathologic parameters and higher regional disease spread, unlike PTC tall cell variant which did not portend worse behavior. The presence of necrosis conferred worse DFS (P=0.006), while increased mitotic activity did not. While the entire HGFCTC group did not correlate with outcome (P=0.071), HGFCTC with necrosis imparted worse DFS (P=0.006). When restricted to PTC-DSV and HGFCTC with necrosis, high-risk histologic classification emerged as an independent prognostic parameter of DFS (P=0.020). The excellent prognosis of pediatric TCs differs from that of adult TCs showing similar histologic features. While neither increased mitotic activity nor PTC tall cell variant histology predict adverse outcome, PTC-DSV and tumors with necrosis constitute high-risk histologic variants with an increased risk of protracted disease.
Binding of respiratory syncytial virus particles to platelets does not result in their degranulation in vitro
Authors: Lakerveld Anke J. , van Erp Elisabeth A. , van Kasteren Puck B.
Published: August 2022

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infection in infants and elderly. The mechanisms behind severe RSV disease are incompletely understood, but a dysregulated immune response likely plays an important role. Platelets are increasingly being recognized as immune cells and are involved in pathology of several viruses. The release of chemokines from platelets upon activation may attract for example neutrophils to the site of infection, which is a hallmark of RSV pathology. In addition, since RSV infections are sometimes associated with cardiovascular events and platelets express several known RSV receptors, we investigated the effect of RSV exposure on platelet degranulation. Washed human platelets were incubated with sucrose-purified RSV particles. P-selectin and CD63 surface expression and CCL5 secretion were measured to assess platelet degranulation. We found that platelets bind and internalize RSV particles, but this does not result in degranulation. Our results suggest that platelets do not play a direct role in RSV pathology by releasing chemokines to attract inflammatory cells.
Nitrite reductase activity in F420-dependent sulfite reductase (Fsr) from Methanocaldococcus jannaschii
Authors: Heryakusuma Christian , Johnson Eric F. , Purwantini Endang , Mukhopadhyay Biswarup
Published: August 2022

Methanocaldococcus jannaschii ( Mj ), a hyperthermophilic and evolutionarily deeply rooted methanogenic archaeon from a deep-sea hydrothermal vent, produces F 420 -dependent sulfite reductase (Fsr). This enzyme allows Mj to detoxify sulfite, a potent inhibitor of methyl coenzyme-M reductase (Mcr), by reducing it to sulfide with reduced coenzyme F 420 (F 420 H 2 ) as electron donor, and to utilize this oxyanion as a sulfur source; Mcr is essential for energy production for a methanogen. Nitrite is another potent inhibitor of Mcr and toxic to methanogens. It is reduced by most sulfite reductases. In this study, we report that Mj Fsr reduced nitrite to ammonia with F 420 H 2 and exhibiting physiologically relevant K m values (nitrite, 8.9 μM; F 420 H 2 , 9.7 μM). The enzyme also reduced hydroxylamine with a K m value of 112.4 μM, indicating that it was an intermediate in the reduction of nitrite to ammonia. These results open the possibility that Mj could use nitrite as a nitrogen source if it is provided at a low concentration of the type that occur in its habitat.
SCsnvcna: Integrating SNVs and CNAs on a phylogenetic tree from single-cell DNA sequencing data
Authors: Zhang Liting , Bass Hank W. , Irianto Jerome , Mallory Xian
Published: August 2022

Single-cell DNA sequencing enables the construction of evolutionary trees that can reveal how tumors gain mutations and grow. Different whole genome amplification (WGA) procedures render genomic materials of different characteristics, often suitable for the detection of either single nucleotide variation (SNV) or for copy number aberration (CNA), but not for both, hindering the placement of both SNVs and CNAs on the same phylogenetic tree for the study of interplay of SNVs and CNAs. SCARLET places SNVs on a CNA tree, a tree derived based on the copy number profiles, while considering SNV loss due to copy number losses. However, SCARLET requires that the SNVs and CNAs are detected from the same sets of cells, which is technically challenging due to the sequencing errors or the low sequencing coverage associated with a particular WGA procedure. Here we presented a novel computational tool, SCsnvcna, that aims at placing SNVs on a CNA tree whereas the sets of cells rendering the SNVs and CNAs are independent, thus is more practical in terms of the technical challenge from single cell WGA process. SCsnvcna is a Bayesian probabilistic model that utilizes both the genotype constraints on the tree and the cellular prevalence (CP) to search the solution that has the highest joint probability. Both simulated and real datasets show that SCsnvcna is highly accurate in predicting the placement of SNVs and SNV cells. In addition, SCsnvcna has a precise prediction of SNV losses due to copy number loss.
Can hyper/hypo-osmoregulating fiddler crabs from the Atlantic coast of South America mobilize intracellular free amino acids as osmotic effectors during salinity challenge?
Authors: Faria Samuel Coelho , McNamara John Campbell
Published: August 2022

Weakly osmoregulating crustaceans use intracellular free amino acids (FAA) to attenuate cell volume changes consequent to alterations in hemolymph osmolality. Whether semi-terrestrial, strong hyper/hypo-osmoregulators exhibit this ability is not known. We investigate FAA mobilization in muscle tissue of ten fiddler crabs from the generaMinuca, LeptucaandUcadistributed along the Atlantic coast of South America. Crabs were subjected to severe hypo- or hyper-osmotic challenge at their upper or lower critical salinity limits for five days; control crabs were held in isosmotic media. Hemolymph osmolality was measured, chela muscle FAA were identified and quantified, and percent contribution to intracellular osmolality (%FAA) was calculated. At isosmoticity, total FAA were nominally 2-fold higher inMinucaspecies (≈116 mmol/kg wet mass) than inUca(≈60 mmol/kg wet mass). Glycine, alanine, arginine and taurine constituted >80% of total FAA. On hyper-osmotic challenge, hemolymph osmolalities ranged from 843 to 1,282 mOsm/kg H2O. FAA increased, although %FAA remained unaltered. Hypo-osmoregulating crabs thus can mobilize FAA, likely owing to a lesser ability to secrete salt near their upper critical limits. On hypo-osmotic challenge, osmolalities were more tightly regulated, between 475 and 736 mOsm/kg H2O. Total FAA and %FAA showed little change, probably due to the crabs’ strong hyper-osmotic extracellular regulation, FAA consequently playing a diminished role in isosmotic intracellular regulation. Total FAA responses to hyper/hypo-osmotic challenge are thus asymmetrical. There was no effect of crab genus on total FAA or on %FAA at isosmoticity or on either osmotic challenge, reinforced by the absence of phylogenetic signal.
Cloud-native distributed genomic pileup operations
Authors: Wiewiórka Marek , Szmurło Agnieszka , Stankiewicz Paweł , Gambin Tomasz
Published: August 2022

Motivation

Pileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computation nodes.

Results

Here, we present a scalable, distributed, and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) our custom data-partitioning algorithm optimized to work with the alignment reads, (ii) a novel and unique approach to process alignment events from sequencing reads using the MD tags, (iii) the source code micro-optimizations for recurrent operations, and (iv) a modular structure of the algorithm. We have proven that our novel approach consistently and significantly outperforms other state-of-the-art distributed tools in terms of execution time (up to 6.5x faster) and memory usage (up to 2x less), resulting in a substantial cloud cost reduction. SeQuiLa is a cloud-native solution that can be easily deployed using any managed Kubernetes and Hadoop services available in public clouds, like Microsoft Azure Cloud, Google Cloud Platform, or Amazon Web Services. Together with the already implemented distributed range joins and coverage calculations, our package provides end-users with an unified SQL interface for convenient analyzing of population-scale genomic data in an interactive way.

Availability

https://biodatageeks.github.io/sequila/

Contact

tomasz.gambin@pw.edu.pl

Supplementary information

Supplementary data are available at Bioinformatics online.
Kinetics-based Inference of Environment-Dependent Microbial Interactions and Their Dynamic Variation
Authors: Song Hyun-Seob , Lee Na-Rae , Kessell Aimee K. , McCullough Hugh C. , Park Seo-Young , Zhou Kang , Lee Dong-Yup
Published: August 2022

Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. This unique capability of our approach was experimentally demonstrated using a synthetic consortium of twoEscherichia colimutants that are metabolically dependent (due to an inability to synthesize essential amino acids), but competitively growing on a shared substrate. The analysis of theE. colibinary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates, but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.

IMPORTANCE

Modeling of environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer complex dynamics of microbial communities. Moreover, robust prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among microorganisms such as plants and animals, as well as microorganisms.
Prioritizing landscapes to reconcile biodiversity conservation, ecosystem services, and human well-being in India
Authors: Srivathsa Arjun , Vasudev Divya , Nair Tanaya , Chakrabarti Stotra , Chanchani Pranav , DeFries Ruth , Deomurari Arpit , Dutta Sutirtha , Ghose Dipankar , Goswami Varun R. , Nayak Rajat , Neelakantan Amrita , Thatte Prachi , Vaidyanathan Srinivas , Verma Madhu , Krishnaswamy Jagdish , Sankaran Mahesh , Ramakrishnan Uma
Published: August 2022

Biodiversity conservation and human well-being are tightly interlinked; yet mismatches in the scale at which both priorities are planned and implemented have exacerbated biodiversity loss, erosion of ecosystem services, and declining human quality of life. India houses the second largest human population on the planet, while <5% of the country’s land area is effectively protected for conservation. This warrants landscape-level conservation planning through a judicious mix ofland-sharingandland-sparingapproaches, and co-production of ecosystem services. Through a multi-faceted assessment, we prioritize spatial extents of land parcels that, in the face of anthropogenic threats, can safeguard conservation landscapes across India’s biogeographic zones. We find that only a fraction (~15%) of such priority areas identified here are encompassed under India’s extant PA network, and several landscapes of high importance were omitted in all previous global-scale assessments. We then examined the spatial congruence of priority areas with administrative units earmarked for economic development by the Indian government, and propose management-zoning through state-driven and participatory approaches. Our spatially explicit insights can help meet the twin goals of biodiversity conservation and sustainable development in India and other countries across the Global South.
Aging Differentially Affects Axonal Autophagosome Formation and Maturation
Authors: Tsong Heather , Holzbaur Erika , Stavoe Andrea KH
Published: August 2022

Misregulation of neuronal autophagy has been implicated in age-related neurodegenerative diseases including Parkinson’s disease and Huntington’s disease. We compared autophagosome formation and maturation in primary murine neurons during development and through aging to elucidate how aging affects neuronal autophagy. We observed an age-related decrease in the rate of formation of LC3B-positive autophagosomes leading to a significant decrease in the density of autophagosomes along the axon. Next, we assessed the maturation of autophagic vesicles and identified a surprising increase in their maturation in neurons from aged mice. While we did not detect notable changes in endolysosomal content in the distal axon during aging, we found that autophagic vesicles were transported more efficiently in neurons from adult mice than in neurons from young mice. This efficient transport of autophagic vesicles in both the distal and proximal axon is maintained in neurons from aged mice and indicates that aging alone does not impair transport nor negatively impact the later stages of autophagy. However, the pronounced deficit in autophagosome biogenesis in aged neurons may contribute to a decreased capacity to clear aggregated proteins or dysfunctional organelles and thus contribute to age-related degeneration.
Co-obligate symbioses have repeatedly evolved across aphids, but partner identity and nutritional contributions vary across lineages
Authors: Manzano-Marín Alejandro , d’acier Armelle Coeur , Clamens Anne-Laure , Cruaud Corinne , Barbe Valérie , Jousselin Emmanuelle
Published: August 2022

Aphids are a large family of phloem-sap feeders. They typically rely on a single bacterial endosymbiont,Buchnera aphidicola, to supply them with essential nutrients lacking in their diet. This association withBuchnerawas described in model aphid species from the Aphidinae subfamily and has been assumed to be representative of most aphids. However, in two lineages,Buchnerahas lost some essential symbiotic functions and is now complemented by additional symbionts. Though these cases break our view of aphids harbouring a single obligate endosymbiont, we know little about the extent, nature, and evolution of these associations across aphid subfamilies. Here, using metagenomics on 25 aphid species from nine subfamilies, re-assembly and re-annotation of 20 aphid symbionts previously sequenced, and 16S rRNA amplicon sequencing on 223 aphid samples (147 species from 12 subfamilies), we show that dual symbioses have evolved anew at least six times. We also show that these secondary co-obligate symbionts have typically evolved from facultative symbiotic taxa. Genome-based metabolic inference confirms interdependencies betweenBuchneraand its partners for the production of essential nutrients but shows contributions vary across pairs of co-obligate associates. Fluorescentin situhybridisation microscopy shows a common bacteriocyte localisation of two newly acquired symbionts. Lastly, patterns ofBuchneragenome evolution reveal that small losses affecting a few key genes can be the onset of these dual systems, while large gene losses can occur without any co-obligate symbiont acquisition. Hence, theBuchnera-aphid association, often thought of as exclusive, seems more flexible, with a few metabolic losses having recurrently promoted the establishment of a new co-obligate symbiotic partner.
The zebrafish dmrt family genes have cooperative and antagonistic roles in sex determination and oogenesis
Authors: Steinfeld Jocelyn S. , Ameyaw Keith K. , Wood Christopher G. , Johnston Ryan M. , Escauriza Ana J. Johnson , Torija Emma G. , Quiles Kiloni , Venkataramani Kavita , MacNeil Jessica N. , Siegfried Kellee R.
Published: August 2022

The double-sex and mab3 related transcription factor (dmrt) gene family has conserved roles in sex determination and gonad development across metazoans. In zebrafish, dmrt1 was previously shown to function in male sex-determination and testes development. To gain a broader knowledge of this gene family in sexual development, we investigated potential roles of all zebrafish dmrt family genes in sex-determination and gonad development using mutant analysis. The dmrt2a and dmrt5 mutants conferred lethality prior to sex differentiation, whereas dmrt2b and dmrt3 mutants were viable and fertile. Dmrt2b mutants had normal sex ratios while dmrt3 showed slightly skewed sex ratios in some experiments, indicating that dmrt3 has a minor role in sex-determination. We report a previously unknown role for dmrt1 in ovary development. Although dmrt1 mutant females were fertile, oogenesis did not progress normally, as evident from abnormal proportions of differently-staged oocytes within mutant ovaries. We also asked if dmrt1 mutant phenotypes could be modified by loss of another dmrt family member. Analysis of dmrt1;dmrt2a mutants was possible as these double mutants were sub-viable, showing a partial rescue of the dmrt2a lethality in the dmrt1 mutant background. The dmrt1;dmrt2a mutants had less severe female bias than dmrt1 mutants suggesting that dmrt2a acts antagonistically to dmrt1 in sex determination. Double mutants of dmrt1 with either dmrt2a or dmrt3 had more severe oogenesis defects than dmrt1 mutants and had either sub-fertility with reduced fecundity or failed to breed, respectively. This study reveals previously unknown roles of zebrafish dmrt1, dmrt2a, and dmrt3 in oogenesis.
Evidence for the Existence of a Bacterial Etiology for Alzheimer’s Disease and for a Temporal-Spatial Development of a Pathogenic Microbiome in the Brain
Authors: Moné Yves , Earl Joshua P. , Król Jarosław E. , Ahmed Azad , Sen Bhaswati , Ehrlich Garth D. , Lapides Jeffrey R.
Published: August 2022

Background

Over the last few decades, a growing body of evidence suggests a role for various infectious agents in Alzheimer’s Disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, or fungi) being detected in AD subjects’ brains, most research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects’ brains.

Results

We obtained post-mortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control aged-matched subjects with a total of 130 samples from the frontal and temporal lobes and entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify the bacteria.

We detected bacteria in the brains of both cohorts with the principal bacteria comprisingPropionibacterium acnes(recently renamedCutibacterium acnes)and two species each ofAcinetobacterandComamonasgenera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances we also employed an unconventional analysis approach that utilized Latent Dirichlet Allocation, often used in computational linguistics. This allowed us to identify 5 classes of samples, each revealing a different microbiome. Assuming that samples represented infections that potentially began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.

Conclusions

The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance ofPropionibacterium acneswith pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included:Methylobacterium, Bacillus, Caulobacter, Delftia,andVariovorax. P. acnesmay also be involved with outcompeting theComamonasspecies, which were strongly associated with non-demented brain microbiome, whose early destruction could be the first stage of the disease. The statistical results are also consistent with a leaky blood brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.
Local Field Potentials, Spiking Activity, and Receptive Fields in Human Visual Cortex
Authors: Luo Lu , Wang Xiongfei , Lu Junshi , Chen Guanpeng , Luan Guoming , Li Wu , Wang Qian , Fang Fang
Published: August 2022

The concept of receptive field (RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals, while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials (LFPs) and spiking activity in human visual cortex (V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from low-frequency activity (LFA, 0.5 – 30 Hz) were larger than those estimated from low-gamma activity (LGA, 30 – 60 Hz) and high-gamma activity (HGA, 60 – 150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.
Redox signaling regulates breast cancer metastasis via HIF1α-stimulated EMT dynamics and metabolic reprogramming
Authors: Ren Zuen , Dharmaratne Malindrie , Liang Huizhi , Benard Outhiriaradjou , Morales-Gallego Miriam , Suyama Kimita , Fard Atefeh Taherian , Mar Jessica C. , Prystowsky Michael , Norton Larry , Hazan Rachel B.
Published: August 2022

Metastasis is orchestrated by phenotypic and metabolic reprogramming underlying tumor aggressiveness. Redox signaling by mammary tumor knockdown (KD) of the antioxidant glutathione peroxidase 2 (GPx2) enhanced metastasis via dynamic changes in epithelial-to-mesenchymal transition. Single cell RNA sequencing (scRNA-seq) of the control and PyMT/GPx2 KD mammary tumor revealed six luminal and one basal/mesenchymal like (cluster 3) subpopulations. Remarkably, GPx2 KD enhanced the size and basal/mesenchymal gene signature of cluster 3 as well as induced epithelial/mesenchymal (E/M) clusters which expressed markers of oxidative phosphorylation and glycolysis, indicative of hybrid metabolism. These data were validated in human breast cancer xenografts and were supported by pseudotime cell trajectory analysis. Moreover, the E/M and M states were both attenuated by GPx2 gain of function or HIF1α inhibition, leading to metastasis suppression. Collectively, these results demonstrate that redox/HIF1α signaling promotes mesenchymal gene expression, resulting in E/M clusters and a mesenchymal root subpopulation, driving phenotypic and metabolic heterogeneity underlying metastasis.

Significance

By leveraging single cell RNA analysis, we were able to demonstrate that redox signaling by GPx2 loss in mammary tumors results in HIF1α signaling, which promotes partial and full EMT conversions, represented by distinct tumor cell subpopulations, which in turn express hybrid and binary metabolic states. These data underscore a phenotypic and metabolic co-adaptation in cancer, arguing in favor of the GPx2-HIF1α axis as a therapeutic platform for targeting tumor cell metastasis.