bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect and mechanism of Jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis
Authors: Tang Yueheng , Su Hao , Wang Hongzhan , Lu Fuer , Nie Kexin , Wang Zhi , Huang Wenya , Dong Hui
Published: December 2021

Background

The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology.

Methods

CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method.

Results

The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc.

Conclusion

Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.
SpinSPJ: a novel NMR scripting system to implement artificial intelligence and advanced applications
Authors: Liu Zao , Chen Zhiwei , Song Kan
Published: December 2021

Background

Software for nuclear magnetic resonance (NMR) spectrometers offer general functionality of instrument control and data processing; these applications are often developed with non-scripting languages. NMR users need to flexibly integrate rapidly developing NMR applications with emerging technologies. Scripting systems offer open environments for NMR users to write custom programs. However, existing scripting systems have limited capabilities for both extending the functionality of NMR software’s non-script main program and using advanced native script libraries to support specialized application domains (e.g., biomacromolecules and metabolomics). Therefore, it is essential to design a novel scripting system to address both of these needs.

Result

Here, a novel NMR scripting system named SpinSPJ is proposed. It works as a plug-in in the Java based NMR spectrometer software SpinStudioJ. In the scripting system, both Java based NMR methods and original CPython based libraries are supported. A module has been developed as a bridge to integrate the runtime environments of Java and CPython. The module works as an extension in the CPython environment and interacts with Java via the Java Native Interface. Leveraging this bridge, Java based instrument control and data processing methods of SpinStudioJ can be called with the CPython style. Compared with traditional scripting systems, SpinSPJ better supports both extending the non-script main program and implementing advanced NMR applications with a rich variety of script libraries. NMR researchers can easily call functions of instrument control and data processing as well as developing complex functionality (such as multivariate statistical analysis, deep learning, etc.) with CPython native libraries.

Conclusion

SpinSPJ offers a user-friendly environment to implement custom functionality leveraging its powerful basic NMR and rich CPython libraries. NMR applications with emerging technologies can be easily integrated. The scripting system is free of charge and can be downloaded by visiting http://www.spinstudioj.net/spinspj.
Five crucial prognostic-related autophagy genes stratified female breast cancer patients aged 40–60 years
Authors: Li Xiaolong , Zhang Hengchao , Liu Jingjing , Li Ping , Sun Yi
Published: December 2021

Background

Autophagy is closely related to the progression of breast cancer. The aim at this study is to establish a prognostic-related model comprised of hub autophagy genes (AGs) to assess patient prognosis. Simultaneously, the model can guide clinicians to make up individualized strategies and stratify patients aged 40–60 years based on risk level.

Methods

The hub AGs were identified with univariate COX regression and LASSO regression. The functions and alterations of these selected AGs were analyzed as well. Moreover, the multivariate COX regression and correlation analysis between hub AGs and clinicopathological parameters were done.

Results

Totally, 33 prognostic-related AGs were obtained from the univariate COX regression (P < 0.05). SERPINA1, HSPA8, HSPB8, MAP1LC3A, and DIRAS3 were identified to constitute the prognostic model by the LASSO regression. The survival curve of patients in the high-risk and low-risk groups was statistically significant (P < 0.05). The 3-year and 5-year ROC displayed that their AUC value reached 0.762 and 0.825, respectively. Stage and risk scores were independent risk factors relevant to prognosis. RB1CC1, RPS6KB1, and BIRC6 were identified as the most predominant mutant genes. It was found that AGs were mainly involved in regulating the endopeptidases synthesis and played important roles in the ErbB signal pathway. SERPIN1, risk score was closely related to the stage (P < 0.05); HSPA8, risk score were closely related to T stag (P < 0.05); HSPB8 was closely related to N stag (P < 0.05).

Conclusions

Our prognostic model had the relatively robust predictive ability on prognosis for patients aged 40–60 years. If the stage was added into the prognostic model, the predictive ability would be more powerful.
Genome-wide and expression analysis of B-box gene family in pepper
Authors: Ma Jing , Dai Jia-xi , Liu Xiao-wei , Lin Duo
Published: December 2021

Background

BBX transcription factors are a kind of zinc finger transcription factors with one or two B-box domains, which partilant in plant growth, development and response to abiotic or biotic stress. The BBX family has been identified in Arabidopsis, rice, tomato and some other model plant genomes.

Results

Here, 24 CaBBX genes were identified in pepper (Capsicum annuum L.), and the phylogenic analysis, structures, chromosomal location, gene expression patterns and subcellular localizations were also carried out to understand the evolution and function of CaBBX genes. All these CaBBXs were divided into five classes, and 20 of them distributed in 11 of 12 pepper chromosomes unevenly. Most duplication events occurred in subgroup I. Quantitative RT-PCR indicated that several CaBBX genes were induced by abiotic stress and hormones, some had tissue-specific expression profiles or differentially expressed at developmental stages. Most of CaBBX members were predicated to be nucleus-localized in consistent with the transient expression assay by onion inner epidermis of the three tested CaBBX members (CaBBX5, 6 and 20).

Conclusion

Several CaBBX genes were induced by abiotic stress and exogenous phytohormones, some expressed tissue-specific and variously at different developmental stage. The detected CaBBXs act as nucleus-localized transcription factors. Our data might be a foundation in the identification of CaBBX genes, and a further understanding of their biological function in future studies.
Clinical relevance of glomerular IgM deposition in patients with lupus nephritis
Authors: Wang Fengmei , Yu Jirong , Zhang Lei , Zhang Yan , Zhang Jie , Liu Bicheng , Yang Xiaowei
Published: December 2021

Background

The aim of the study was to investigate the clinical relevance of IgM deposition in patients with lupus nephritis (LN) in a large cohort.

Results

217 patients with renal biopsy-proven active LN were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r =  − 0.138, P = 0.043; r =  − 0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributed to glomerular C3 deposition in patients with LN (OR = 2.002, 95% CI 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0–2+ had similar plasma CFH levels, but in patients with IgM3+–4+, plasma CFH levels were significantly lower (300.4 ± 155.8 μg/mL vs. 429.9 ± 187.5 μg/mL, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1 g/d vs. 4.7 ± 3.5 g/d, P = 0.037; 150.1 ± 121.0 μmol/L vs. 105.6 ± 97.1 μmol/L, P = 0.005; 0.3 ± 0.2 μg/L vs. 0.4 ± 0.2 μg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH.

Conclusions

Our results suggested the involvement of glomerular deposited IgM in complement activation and renal injury in LN.
Antagonistic activity of endophytic actinobacteria from native potatoes (Solanum tuberosum subsp. tuberosum L.) against Pectobacterium carotovorum subsp. carotovorum and Pectobacterium atrosepticum
Authors: Padilla-Gálvez Natalia , Luengo-Uribe Paola , Mancilla Sandra , Maurin Amandine , Torres Claudia , Ruiz Pamela , France Andrés , Acuña Ivette , Urrutia Homero
Published: December 2021

Background

The native potatoes (Solanum tuberosum subsp. tuberosum L.) grown in Chile (Chiloé) represent a new, unexplored source of endophytes to find potential biological control agents for the prevention of bacterial diseases, like blackleg and soft rot, in potato crops.

Result

The objective of this study was the selection of endophytic actinobacteria from native potatoes for antagonistic activity against Pectobacterium carotovorum subsp. carotovorum and Pectobacterium atrosepticum, and their potential to suppress tissue maceration symptoms in potato tubers. This potential was determined through the quorum quenching activity using a Chromobacterium violaceaum ATCC 12472 Wild type (WT) bioassay and its colonization behavior of the potato plant root system (S. tuberosum) by means of the Double labeling of oligonucleotide probes for fluorescence in situ hybridization (DOPE-FISH) targeting technique. The results showed that although Streptomyces sp. TP199 and Streptomyces sp. A2R31 were able to inhibit the growth of the pathogens, only the Streptomyces sp. TP199 isolate inhibited Pectobacterium sp. growth and diminished tissue maceration in tubers (p ≤ 0.05). Streptomyces sp. TP199 had metal-dependent acyl homoserine lactones (AHL) quorum quenching activity in vitro and was able to colonize the root endosphere 10 days after inoculation.

Conclusions

We concluded that native potatoes from southern Chile possess endophyte actinobacteria that are potential agents for the disease management of soft rot and blackleg.
Prognosis in patients with coronary heart disease and breath-holding limitations: a free-breathing cardiac magnetic resonance protocol at 3.0 T
Authors: Wang Keyan , Zhang Wenbo , Li Shuman , Bi Xiaoming , Schmidt Michaela , An Jing , Zheng Jie , Cheng Jingliang
Published: December 2021

Background and purpose

Conventional cardiac magnetic resonance (CCMR) imaging is usually performed with breath-holding (BH), which is adverse in patients with BH limitations. We explored the ability of a free-breathing CMR (fCMR) protocol to prognosticate in patients with coronary heart diseases (CHD) and limited BH ability.

Methods

Sixty-seven patients with CHD and limited BH abilities were prospectively enrolled in this study. All patients underwent comprehensive fCMR imaging at 3.0 T. The fCMR protocols included compressed sensing (CS) single-shot cine acceleration imaging, and motion-corrected (MOCO), single-shot late gadolinium enhancement (LGE) imaging. Image quality (IQ) of the cine and LGE images was evaluated based on the 5-point Likert scale. The value of fMRI in providing a prognosis in patients with CHD was assessed. Statistical methods included the T test, Mann–Whitney test, Kappa test, Kaplan–Meier curve, Log-rank test, Cox proportional hazard regression analysis, and receiver operating characteristic curves.

Results

All IQ scores of the short axis CS-cine and both the short and long axes MOCO LGE images were ≥ 3 points. Over a median follow-up of 31 months (range 3.8–38.2), 25 major adverse cardiovascular events (MACE) occurred. In the univariate analysis, infarction size (IS), left ventricular ejection fraction (LVEF), 3D-Global peak longitudinal strain (3D-GPLS), heart failure classification were significantly associated with MACE. When the significantly univariate MACE predictors, added to the multivariate analysis, which showed IS (HR 1.02; 95% CI 1.00–1.05; p = 0.048) and heart failure with preserved EF (HR 0.20; 95% CI 0.04–0.98; p = 0.048) correlated positively with MACE. The optimal cutoff value for LVEF, 3D-GPLS, and IS in predicting MACE was 34.2%, − 5.7%, and 26.1% respectively, with a sensitivity of 90.5%, 64%, and 96.0% and specificity of 72%, 95.2%, and 85.7% respectively.

Conclusions

The fCMR protocol can be used to make prognostic assessments in patients with CHD and BH limitations by calculating IS and LVEF.
Helicobacter pylori infection is associated with reduced risk of Barrett’s esophagus: a meta-analysis and systematic review
Authors: Du Yan-Lin , Duan Ru-Qiao , Duan Li-Ping
Published: December 2021

Background

Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett’s esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship.

Methods

We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies.

Results

46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51–0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15–0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82–1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25–0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78–1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54–0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43–1.78; P = 0.73).

Conclusions

Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.
Hypercortisolism in patients with cholestasis is associated with disease severity
Authors: Theiler-Schwetz Verena , Schlager Hansjörg , Obermayer-Pietsch Barbara , Stojakovic Tatjana , Fauler Günter , Fickert Peter , Zollner Gernot
Published: December 2021

Background

Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis.

Methods

Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry.

Results

Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels.

Conclusions

We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.
mNGS helped diagnose scrub typhus presenting as a urinary tract infection with high D-dimer levels: a case report
Authors: Liu Mei-fang , Liu Yong , Xu De-rong , Wan La-gen , Zhao Rui
Published: December 2021

Background

Scrub typhus is caused by O. tsutsugamushi and spreads through mite larvae biting the skin. Classic symptoms of the disease are eschar and lymphadenopathy. Previous reports have revealed clinical manifestations of scrub typhus, including gastrointestinal symptoms, meningoencephalitis, ocular flutter, pneumonitis, acute respiratory distress syndrome, and acute kidney injury. However, cases of scrub typhus presenting as a urinary tract infection (UTI) with high D-dimer levels could be easily misdiagnosed when clinical attention is insufficient, resulting in difficulty in making a timely diagnosis of the infection. Metagenomics next-generation sequencing (mNGS) is a revolutionary and highly sensitive method that may help in diagnosing atypical cases, even when trace amounts of pathogens are present.

Case presentation

A 52-year-old female presented with a 10-day history of fever, chills, headache and myalgia. She was initially diagnosed with influenza at a local clinic. Various antibacterials were used on the 2nd–12th day onwards; however, her symptoms persisted and were followed by increased urination duration, frequency, urgency and dysuria for 2 days. Orientia tsutsugamushi was confirmed as the pathogen responsible for the infection through mNGS analysis of her blood samples from Day 13 onwards. The patient’s temperature changed remarkably 24 h after the initiation of doxycycline. Over the next 48 h (i.e., Day 15 onwards), the patient showed clinical improvement. She recovered and was discharged from the hospital.

Conclusions

Scrub typhus can present atypical clinical symptoms, such as UTIs, in a febrile patient. mNGS may be a useful method for identifying O. tsutsugamushi infection in patients with atypical clinical manifestations.
Musculoskeletal actinomycosis in children: a case report
Authors: Mou Yani , Jiao Qin , Wang Yizhong , Li Xiaolu , Xiao Yongmei , Zhao Lihua , Zhang Ting
Published: December 2021

Background

Actinomycosis is a rare infectious disease caused by Actinomyces, especially in children. Here, we present a case of musculoskeletal actinomycosis in a 5-year-old girl from China.

Case presentation

A 5-year-old girl presented with recurrent episodes of fever, pain, erythema, swelling, and festering sores on the right lower extremity, and pus was discharged from a sinus in the right foot. Magnetic resonance imaging (MRI) suggested subcutaneous soft tissue infection and osteomyelitis of the right crus. A bacterial culture of pus extracted from a festering sore on the right popliteal fossa detected the growth of Actinomycetes europaeus. The patient was cured with 7 weeks of treatment with intravenous ampicillin-sulbactam, followed by 6 weeks of treatment with oral amoxicillin-clavulanate with surgical debridement and drainage. There were no symptoms of recurrence during the 15-month period of follow-up.

Conclusions

Pediatric actinomycosis is a rare and challenging infectious disease. Early accurate diagnosis and optimal surgical debridement are important for the management of pediatric actinomycosis.
Amputation of a type II diabetic patient with cutaneous leishmaniasis due to Leishmania major
Authors: Izri Arezki , Bendjaballah-Laliam Amina , Sereno Denis , Djenad Ihcene Kherachi , Harrat Zoubir , Akhoundi Mohammad
Published: December 2021

Background

Leishmaniases are neglected tropical diseases of public health concern in Algeria. The immunocompromised patients with HIV, autoimmune diseases, or chronic alcohol abuse are at a higher risk of leishmaniasis. Herein, we present the case of an immunocompetent diabetic patient infected by Leishmania major, leading to life-threatening consequences.

Case presentation

An Algerian diabetic patient developed a cutaneous lesion with large polymorphous inflamed granuloma and pyoderma gangrenosum in the left foot, following L. major infection. A delayed follow-up led to a treatment failure, resulting in the amputation.

Conclusions

This report highlights the absence of timely treatment of Leishmania infection as a life-threatening point among high-risk diabetic patients. Clinicians should be aware of this parasitosis leading to severe complications in diabetic patients.
Evaluation of treatment with two weeks of doxycycline on macrolide-resistant strains of Mycoplasma genitalium: a retrospective observational study
Authors: Gossé M. , Nordbø S. A. , Pukstad B.
Published: December 2021

Background

Increasing macrolide resistance makes treatment of Mycoplasma genitalium infections challenging. The second-line treatment is moxifloxacin, an antibiotic drug best avoided due to the potential of severe side effects and interactions. This study evaluates the effects of treatment with doxycycline 100 mg twice daily for 2 weeks as an alternative to moxifloxacin.

Methods

This retrospective observational study examined the medical records of patients testing positive for macrolide resistant Mycoplasma genitalium from January 1st, 2016 to September 1st, 2019 in Trondheim, Norway. Information regarding symptoms as well as clinical and microbiological cure was collected.

Results

263 infections from 259 patients (161 females/98 males) were examined. 155 (58.9%) had a negative test of cure following treatment. 34.7% of symptomatic patients not achieving microbiological cure experienced symptom relief or clearance. There was no statistical difference between bacterial loads in symptomatic versus asymptomatic patients. The mean difference was 1.6 × 105 copies/ml (95% CI − 1.4 × 105–4.8 × 105, p = 0.30) for women and 1.4 × 106 copies/ml (95% CI -4.0 × 105–3.2 × 106, p = 0.12) for men.

Conclusions

The cure rate of doxycycline in this study is higher than previously reported. This adds support to doxycycline’s role in treatment before initiating treatment with less favorable drugs such as moxifloxacin.
Two cases of multi-inflammatory syndrome in children (MIS-C) in adults in 2020
Authors: Ciochetto Zachary , Havens Peter L. , Aldrete Sol
Published: December 2021

Background

Late complications and longer-lasting sequelae of COVID-19 infection in adults can occur. Cardiovascular involvement including reduced ejection fraction, coronary artery aneurysms, and pericardial involvement have been reported. Prompt recognition is the first step and secondly, these cardiovascular phenomena require an alternative set of therapeutics from the standard of care for acute COVID-19 infection.

Case presentation

Here we describe two cases that fulfill the current case definition of the recently defined multisystem inflammatory syndrome in adults (MIS-A). One patient is a 27-year-old white female and the other a 21-year-old French creole male, both without any prior medical history. Both were hospitalized and found to have significant cardiac dysfunction and treated with IVIG, high dose aspirin, and corticosteroids with resolution of their acute illnesses and cardiac sequelae.

Conclusion

Not only does the immediate impact of this viral infection need to be addressed, but also the long-term complications that could arise if not recognized and treated promptly as seen in our two cases. Patients can develop acute cardiovascular collapse and cardiogenic shock which requires high level of care and treatment within an intensive care unit. Depending on the complications, patients may require treatment for congestive heart failure, pericarditis, or even coronary artery disease acutely with close follow up to ensure improvement or resolution.
Metagenomic next-generation sequencing in the diagnosis of leptospirosis presenting as severe diffuse alveolar hemorrhage: a case report and literature review
Authors: Chen Meiqin , Lu Weili , Wu Shugen , Wang Shun , Lu Tao , Peng Chunxian
Published: December 2021

Background

Leptospirosis is a common infectious disease in tropical and semitropical regions, and it is typically neglected. Leptospirosis-associated acute diffuse alveolar hemorrhage is one of its fatal complications. The use of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing in the diagnosis of Leptospira interrogans infection has rarely been reported.

Case presentation

We present the case of a 62-year-old female who was transferred to our hospital with dyspnea, and severe hemoptysis and was supported by a tracheal intubation ventilator. Bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) reported Leptospira interrogans. A diagnosis of diffuse alveolar hemorrhage caused by leptospirosis was made. After immediately receiving antibiotics and hormone therapy, the patient achieved a complete recovery upon discharge.

Conclusion

Leptospirosis presenting as severe diffuse alveolar hemorrhage is rare but should be considered in the differential diagnosis. mNGS can help identify pathogens and treat them early, which can improve prognosis.
Provider perspectives on the acceptability and tolerability of dolutegravir-based anti-retroviral therapy after national roll-out in Uganda: a qualitative study
Authors: Zakumumpa Henry , Kitutu Freddy Eric , Ndagije Helen Byomire , Diana Nakitto-Kesi , Ssanyu Jacquellyn Nambi , Kiguba Ronald
Published: December 2021

Background

The World Health Organization recommends dolutegravir (DTG) as the for first-line and second-line antiretroviral therapy (ART) worldwide. However, little is known about the acceptability and tolerability of DTG-based ART at routine points-of-care in Uganda. We set out to explore the perceptions of clinicians in ART clinics regarding the acceptability and tolerability of DTG-based ART since national roll-out in March 2018 in Uganda.

Methods

We adopted a qualitative exploratory design involving 49 participants. Between September 2020 and February 2021, we conducted 22 in-depth interviews with clinicians in the ART clinics of 12 purposively selected health facilities across Uganda. The selection of study sites ensured diversity in facility ownership-type (public/private), level of service delivery (tertiary/secondary/primary) and the four major geographic sub-regions of Uganda. We conducted three focus group discussions with 27 clinicians in the participating facilities. Data were analyzed by thematic approach.

Results

Clinicians in ART clinics acknowledged that DTG-based ART is well tolerated by the majority of their patients who appreciate the reduced pill burden, perceived less side effects and superior viral load suppression. However, they reported that a number of their patients experience adverse drug reactions (ADRs) after being transitioned to DTG. Hyperglycemia is, by far, the most commonly reported suspected ADR associated with DTG-based regimens and was cited in all but two participating facilities. Insomnia, weight gain and reduced libido are among the other frequently cited suspected ADRs. In addition, clinicians in ART clinics perceived some of the suspected ADRs as resulting from drug interactions between dolutegravir and isoniazid. Weak diagnostic capacities and shortage of associated commodities (e.g. glucometers and test kits) were reported as impediments to understanding the full extent of ADRs associated DTG-based ART.

Conclusion

While DTG-based regimens were perceived by clinicians in ART clinics to be well tolerated by the majority of their patients, they also reported that a number of patients experience suspected ADRs key among which were hyperglycemia, insomnia and reduced libido. Based on the perspectives of clinicians, we recommend that future studies examine the prevalence of dolutegravir-induced hyperglycemia in patients in Uganda.
A Bayesian network based study on determining the relationship between job stress and safety climate factors in occurrence of accidents
Authors: Khoshakhlagh Amir Hossein , Yazdanirad Saeid , Kashani Masoud Motalebi , Khatooni Elham , Hatamnegad Yaser , Kabir Sohag
Published: December 2021

Background

Job stress and safety climate have been recognized as two crucial factors that can increase the risk of occupational accidents. This study was performed to determine the relationship between job stress and safety climate factors in the occurrence of accidents using the Bayesian network model.

Methods

This cross-sectional study was performed on 1530 male workers of Asaluyeh petrochemical company in Iran. The participants were asked to complete the questionnaires, including demographical information and accident history questionnaire, NIOSH generic job stress questionnaire, and Nordic safety climate questionnaire. Also, work experience and the accident history data were inquired from the petrochemical health unit. Finally, the relationships between the variables were investigated using the Bayesian network model.

Results

A high job stress condition could decrease the high safety climate from 53 to 37% and increase the accident occurrence from 72 to 94%. Moreover, a low safety climate condition could increase the accident occurrence from 72 to 93%. Also, the concurrent high job stress and low safety climate could raise the accident occurrence from 72 to 93%. Among the associations between the job stress factor and safety climate dimensions, the job stress and worker’s safety priority and risk non-acceptance (0.19) had the highest mean influence value.

Conclusion

The adverse effect of high job stress conditions on accident occurrence is twofold. It can directly increase the accident occurrence probability and in another way, it can indirectly increase the accident occurrence probability by causing the safety climate to go to a lower level.
Deep learning computer-aided detection system for pneumonia in febrile neutropenia patients: a diagnostic cohort study
Authors: Hwang Eui Jin , Lee Jong Hyuk , Kim Jae Hyun , Lim Woo Hyeon , Goo Jin Mo , Park Chang Min
Published: December 2021

Background

Diagnosis of pneumonia is critical in managing patients with febrile neutropenia (FN), however, chest X-ray (CXR) has limited performance in the detection of pneumonia. We aimed to evaluate the performance of a deep learning-based computer-aided detection (CAD) system in pneumonia detection in the CXRs of consecutive FN patients and investigated whether CAD could improve radiologists’ diagnostic performance when used as a second reader.

Methods

CXRs of patients with FN (a body temperature ≥ 38.3 °C, or a sustained body temperature ≥ 38.0 °C for an hour; absolute neutrophil count < 500/mm3) obtained between January and December 2017 were consecutively included, from a single tertiary referral hospital. Reference standards for the diagnosis of pneumonia were defined by consensus of two thoracic radiologists after reviewing medical records and CXRs. A commercialized, deep learning-based CAD system was retrospectively applied to detect pulmonary infiltrates on CXRs. For comparing performance, five radiologists independently interpreted CXRs initially without the CAD results (radiologist-alone interpretation), followed by the interpretation with CAD. The sensitivities and specificities for detection of pneumonia were compared between radiologist-alone interpretation and interpretation with CAD. The standalone performance of the CAD was also evaluated, using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Moreover, sensitivity and specificity of standalone CAD were compared with those of radiologist-alone interpretation.

Results

Among 525 CXRs from 413 patients (52.3% men; median age 59 years), pneumonia was diagnosed in 128 (24.4%) CXRs. In the interpretation with CAD, average sensitivity of radiologists was significantly improved (75.4% to 79.4%, P = 0.003) while their specificity remained similar (75.4% to 76.8%, P = 0.101), compared to radiologist-alone interpretation. The CAD exhibited AUC, sensitivity, and specificity of 0.895, 88.3%, and 68.3%, respectively. The standalone CAD exhibited higher sensitivity (86.6% vs. 75.2%, P < 0.001) and lower specificity (64.8% vs. 75.4%, P < 0.001) compared to radiologist-alone interpretation.

Conclusions

In patients with FN, the deep learning-based CAD system exhibited radiologist-level performance in detecting pneumonia on CXRs and enhanced radiologists’ performance.
Bone damage after chemotherapy for lymphoma: a real-world experience
Authors: Mancuso S. , Scaturro Dalila , Santoro M. , Di Gaetano G. , Vitagliani F. , Falco V. , Siragusa S. , Gonnelli S. , Mauro G. Letizia
Published: December 2021

Background

Despite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures.

Aim

To provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy.

Method

A cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques and screening tools for the assessment of functional status and quality of life (SARC-F and mini-Osteoporosis Quality of Life).

Results

Approximately 50% of patients had osteoporosis, with a prevalence of vertebral fractures of 65.5%. In most patients, we found hypovitaminosis D and high levels of parathyroid hormone (PTH). Furthermore, a statistically significant association was observed between high PTH levels and previous lymphoma treatment. Finally, the Mini-Osteoporosis Quality of life (mini-OQLQ) questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status.

Conclusions

Patient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients.
Aesthetic monitoring-based assessment of oncological safety of oncoplastic management of breast cancer: a multi-center research study
Authors: Awad Selmy , Tarabay Ahmed , Qahtani Fahad H. , Alsulaimani Faisal S. , Shaat Mohamed M. , Ali Mazin A. , Khalid Ahmad H. , Alharthi Qasem M. , ALThomali Musab A. , Althobaiti Shabab S. , AlAmri Nadiah G. , Alturkistani Abdullah M. , Alshamrani Abdullah A. , Ali Amal A. , Alsufyani Ahmed H. , AlSofyani Fahad M. , Alghuraybi Abdullah A. , Alnefaie Amer M. , Alharthi Shuruq A. , Almalki Abdulrahman A. , Alghamdi Abdulrahman S. , Alzahrani Azzah , Yehia Ashraf , Abou Sheishaa Mohamed Samir
Published: December 2021

Background

Oncoplastic Breast surgeries (OBS) in breast cancer have evolved to preserve the cancerous breast rather than its amputation to improve postoperative cosmetic results. The lack of evidence to support the oncological safety and benefits of OBS is questionable. In this study, we evaluate various aspects of oncoplastic surgeries with a focused monitoring of aesthetic results and oncological safety.

Methods

This was a multi-center observational study focused on the statistics of data collected from cases who underwent oncoplastic surgeries from the cohort of breast cancer candidates at Mansoura University Hospitals/Egypt and King Faisal Medical Complex/KSA from January 2015 to June 2018. All data were analyzed carefully using SPSS v-26.

Results

Eighty cases who underwent different oncoplastic surgeries were included and reviewed for the aesthetic outcome and oncological safety. The recurrence rate was found to be 2.5%. The breast impact treatment scale assessment method was used to analyze the aesthetic outcomes, and average scores were accepted in 90% of patients.

Conclusions

The oncoplastic breast surgeries are feasible and they had a high rate of oncological safety with the maintenance of good aesthetic outcomes and patient satisfaction.
Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis
Authors: Gheinani Ali Hashemi , Akshay Akshay , Besic Mustafa , Kuhn Annette , Keller Irene , Bruggmann Rémy , Rehrauer Hubert , Adam Rosalyn M. , Burkhard Fiona C. , Monastyrskaya Katia
Published: December 2021

Background

Interstitial cystitis, or bladder pain syndrome (IC/BPS), is a chronic bladder disorder characterized by lower abdominal pain associated with the urinary bladder and accompanied by urinary frequency and urgency in the absence of identifiable causes. IC/PBS can be separated into the classic Hunner’s ulcerative type and the more prevalent non-ulcerative disease. Our aim was to unravel the biological processes and dysregulated cell signaling pathways leading to the bladder remodeling in non-ulcerative bladder pain syndrome (BPS) by studying the gene expression changes in the patients’ biopsies.

Methods

We performed paired microRNA (miRNA) and mRNA expression profiling in the bladder biopsies of BPS patients with non-Hunner interstitial cystitis phenotype, using comprehensive Next-generation sequencing (NGS) and studied the activated pathways and altered biological processes based on the global gene expression changes. Paired mRNA-miRNA transcriptome analysis delineated the regulatory role of the dysregulated miRNAs by identifying their targets in the disease-induced pathways.

Results

EIF2 Signaling and Regulation of eIF4 and p70S6K Signaling, activated in response to cellular stress, were among the most significantly regulated processes during BPS. Leukotriene Biosynthesis nociceptive pathway, important in inflammatory diseases and neuropathic pain, was also significantly activated. The biological processes identified using Gene Ontology over-representation analysis were clustered into six main functional groups: cell cycle regulation, chemotaxis of immune cells, muscle development, muscle contraction, remodeling of extracellular matrix and peripheral nervous system organization and development. Compared to the Hunner’s ulcerative type IC, activation of the immune pathways was modest in non-ulcerative BPS, limited to neutrophil chemotaxis and IFN-γ-mediated signaling. We identified 62 miRNAs, regulated and abundant in BPS and show that they target the mRNAs implicated in eIF2 signalling pathway.

Conclusions

The bladders of non-ulcerative BPS patients recruited in this study had alterations consistent with a strong cell proliferative response and an up-regulation of smooth muscle contractility, while the contribution of inflammatory processes was modest. Pathway analysis of the integrated mRNA-miRNA NGS dataset pinpointed important regulatory miRNAs whose dysregulation might contribute to the pathogenesis. Observed molecular changes in the peripheral nervous system organization and development indicate the potential role of local bladder innervation in the pain perceived in this type of BPS.
Antibacterial effect of cerium oxide nanoparticle against Pseudomonas aeruginosa
Authors: Zamani Khosro , Allah-Bakhshi Noushin , Akhavan Faezeh , Yousefi Mahdieh , Golmoradi Rezvan , Ramezani Moazzameh , Bach Horacio , Razavi Shabnam , Irajian Gholam-Reza , Gerami Mahyar , Pakdin-Parizi Ali , Tafrihi Majid , Ramezani Fatemeh
Published: December 2021

Background

Antibiotics have been widely used for the treatment of bacterial infections for decades. However, the rapid emergence of antibiotic-resistant bacteria has created many problems with a heavy burden for the medical community. Therefore, the use of nanoparticles as an alternative for antibacterial activity has been explored. In this context, metal nanoparticles have demonstrated broad-spectrum antimicrobial activity. This study investigated the antimicrobial activity of naked cerium oxide nanoparticles dispersed in aqueous solution (CNPs) and surface-stabilized using Pseudomonas aeruginosa as a bacterial model.

Methods

Gelatin-polycaprolactone nanofibers containing CNPs (Scaffold@CNPs) were synthesized, and their effect on P. aeruginosa was investigated. The minimum inhibitory and bactericidal concentrations of the nanoparticls were determined in an ATCC reference strain and a clinical isolate strain. To determine whether the exposure to the nanocomposites might change the expression of antibiotic resistance, the expression of the genes shv, kpc, and imp was also investigated. Moreover, the cytotoxicity of the CNPs was assessed on fibroblast using flow cytometry.

Results

Minimum bactericidal concentrations for the ATCC and the clinical isolate of 50 µg/mL and 200 µg/mL were measured, respectively, when the CNPs were used. In the case of the Scaffold@CNPs, the bactericidal effect was 50 µg/mL and 100 µg/mL for the ATCC and clinical isolate, respectively. Interestingly, the exposure to the Scaffold@CNPs significantly decreased the expression of the genes shv, kpc, and imp.

Conclusions

A concentration of CNPs and scaffold@CNPs higher than 50 μg/mL can be used to inhibit the growth of P. aeruginosa. The fact that the scaffold@CNPs significantly reduced the expression of resistance genes, it has the potential to be used for medical applications such as wound dressings.
Oral cancer among Khat users: finding evidence from DNA analysis of nine cancer-related gene mutations
Authors: Alshahrani Sawsan Abdullah , Al-Qahtani Wedad Saeed , Almufareh Nawaf Abdulrahman , Domiaty Dalia Mostafa , Albasher Gadah Ibraheem , Safhi Fatmah Ahmed , AlQassim Fatima Abdullah , Alotaibi Mashael Alhumaidi , Al-Hazani Tahani Mohamed , Almutlaq Bassam Ahmed
Published: December 2021

Background

Khat leaves contain the alkaloid cathinone. Research shows that khat might provoke toxicity, mutagenicity, as well as carcinogenicity.

Methods

Two groups were identified as khat abusers and were categorized by abuse time and diagnosis of oral squamous cell carcinoma (OSCC). Here, 41 participants from Group 2 were short-term khat users, and 42 participants were long-term khat users. The control group included 30 healthy individuals.

The coding exons included nine cancer-related genes and were analysed. The histopathological research was conducted with H&E staining along with the TP53 protein expression by implementing immunohistochemical analyses.

Results

Here, 41 short-term khat users carried seven somatic mutations in four out of nine cancer-related genes: 29/41(70.73%)ARID1A, 24/41(58.53%)MLH1, 34/41(82.92%)PIK3CAand 36/41(87.80%)TP53. The 42 long-term khat users incorporated nine somatic mutations in five out of nin ecancer-related genes: 40/42(95.23%)ARID1A, 36/42(85.71%)ARID2, 29/42(69.04%)PIK3CA, 27/42(64.28%)MLH1, and 35/42(83.33%)TP53. Every khat user had somatic mutations related to OSCC affecting the gingiva and the lower lip. TP53 protein expression was confirmed in all immunohistochemical oral tests. Carcinoma was also positive in the histopathological analysis.

Conclusions

Khat is a mutagenic and carcinogenic plant that provoked OSCC among short-term khat users (<15 years of use) and long-term users (>15 years of use).