bluuebunny/crossref_metadata_2025 huggingface dataset:
Menopause Rating Scale (MRS) in the Malay language-translation and validation in a multiethnic population of Selangor, Malaysia
Authors: Mathialagan Sashimalar , Ramasamy Shamala , Nagandla Kavitha , Siew Wei Fern , Sreeramareddy Chandrashekhar T.
Published: August 2022

Background

The Menopause Rating Scale (MRS) is an internationally used tool to measure menopause-related symptoms and to date it is unavailable in the Malay language. We aimed to translate and validate the Malay language version of the MRS.

Methods

Translation of the English version of MRS into Malay was done by a bilingual expert and back translated. Translated version of MRS was reviewed by a panel to determine the face validity. A sample of 321 women aged 40–60 years residing in Klang, Selangor, Malaysia was selected by stratified random sampling method in a house-to-house survey. The Malay language version of MRS was self-administered. Reliability analyses, including test–retest reliability (on 30 women after a two-week interval) were conducted. To ascertain the construct validity, 11 items were analyzed confirmatory factor analysis was conducted to evaluate the structural model fit of the Malay language version of MRS.

Results

A total of 294 (91.6%) completed the survey and their mean age was 50.9 years (SD = 6.3). An overall Cronbach’s alpha for MRS was 0.904. Cronbach’s alpha for psychosomatic, urogenital, and somatovegetative subscales were 0.889, 0.846, and 0.776 respectively. The corrected item correlations were approximately 0.6 and inter-item correlations were between 0.3 and 0.9. On exploratory structural equation modelling, the chi-square test of goodness of fit yielded a significant value; χ2 = 78.4, df = 25, p < 0.001, (reported if N > 200). Additionally, the value of Tucker–Lewis Index (TLI) = 0.954showed a good fit to the model.

Conclusion

The translated English version of the Menopause Rating Scale into the Malay language showed excellent reliability, test–retest reliability, and construct validity. The instrument can be used to assess menopause-related symptoms among Malaysian women.
A randomized controlled trial of WeChat-based cognitive behavioral therapy intervention to improve cancer-related symptoms in gynecological cancer survivors: study protocol
Authors: Sun Liyuan , Tao Yanling , Zhu Shening , Liu Ke
Published: August 2022

Background

Gynecological malignant patients often have significant psychological and physical problems. The feasibility and generalizability of traditional intervention method is low due to the high time and labor cost, large number of gynecological malignant tumor patients in China, as well as shortage of health professionals. Therefore, it is necessary to design an alternative, innovative, and easily accessible intervention method. This study aims to evaluate the effect of WeChat-based intervention on anxiety, depression and disease-related symptoms of patients with gynecological malignant tumors during rehabilitation.

Methods

A single-blinded, randomized, controlled, parallel-group pre-test and repeated post-test design will be conducted. A total of 76 participants will be randomly divided into the intervention group and control group. Anxiety and depression, disease-related symptoms, coping ability, benefit finding and quality of life will be measured at baseline and repeated immediately after the intervention (test 1), 3 months (test 2) and 6 months (test 3) after the intervention.

Discussion

As the first randomized controlled trial with rigorous research design for patients with gynecological malignant tumors in the rehabilitation stage in China, this study will provide evidences for the effectiveness of the WeChat platform during intervention of patients with gynecological malignant tumors in the rehabilitation stage. The results are helpful to further explore the effect of WeChat-based intervention on improving patients' anxiety and depression, disease-related symptoms, and quality of life.

Trial registration

Chinese Clinical Trial Registry: ChiCTR2100053450, Registered 21 November 2021,http://www.chictr.org.cn/searchproj.aspx
Production of new antimicrobial palm oil-derived sophorolipids by the yeast Starmerella riodocensis sp. nov. against Candida albicans hyphal and biofilm formation
Authors: Alfian Achmad Rifky , Watchaputi Kwanrutai , Sooklim Chayaphathra , Soontorngun Nitnipa
Published: August 2022

Background

Microbial derived-surfactants display low eco-toxicity, diverse functionality, high biodegradability, high specificity, and stability under extreme conditions. Sophorolipids are emerging as key biosurfactants of yeast origins, used in various industrial sectors to lower surface tension. Recently, sophorolipid complexes have been applied in biomedicals and agriculture to eradicate infectious problems related to human and plant fungal pathogens. This study aimed to characterize the functional properties and antifungal activities of sophorolipids produced by a newly characterized Starmerella riodocensis GT-SL1R sp. nov. strain.

Results

Starmerella riodocensis GT-SL1R sp. nov. strain was belonged to Starmerella clade with 93.12% sequence similarity using the ITS technique for strain identification. Sophorolipids production was examined, using co-carbon substrates glucose and palm oil, with a yield on the substrate between 30 and 46%. Using shake-flasks, the S. riodocensis GT-SL1R strain produced biosurfactants with an emulsification activity of 54.59% against kerosene compared to the S. bombicola BCC5426 strain with an activity of 60.22%. Maximum productivities of GT-SL1R and the major sophorolipid-producer S. bombicola were similar at 0.8 gl−1 h−1. S. riodocensis GT-SL1R produced mixed forms of lactonic and acidic sophorolipids, shown by TCL, FTIR, and HPLC. Importantly, the complex sophorolipid mixture displayed antifungal activity against an opportunistic yeast pathogen Candida albicans by effectively reducing hyphal and biofilm formation.

Conclusions

Sophorolipids derived from S. riodocensis demonstrate potential industrial and biomedical applications as green surfactant and antifungal agent. Since numerous renewable bioresources and industrial wastes could be used by microbial cell factories in the biosynthesis of biosurfactants to reduce the production cost, sophorolipids hold a promising alternative to current antimicrobials in treatments against infectious diseases in humans, animals, and plants.
Human growth hormone inclusion bodies present native-like secondary and tertiary structures which can be preserved by mild solubilization for refolding
Authors: Chura-Chambi Rosa Maria , Farah Chuck Shaker , Morganti Ligia
Published: August 2022

Background

Native-like secondary structures and biological activity have been described for proteins in inclusion bodies (IBs). Tertiary structure analysis, however, is hampered due to the necessity of mild solubilization conditions. Denaturing reagents used for IBs solubilization generally lead to the loss of these structures and to consequent reaggregation due to intermolecular interactions among exposed hydrophobic domains after removal of the solubilization reagent. The use of mild, non-denaturing solubilization processes that maintain existing structures could allow tertiary structure analysis and increase the efficiency of refolding.

Results

In this study we use a variety of biophysical methods to analyze protein structure in human growth hormone IBs (hGH-IBs). hGH-IBs present native-like secondary and tertiary structures, as shown by far and near-UV CD analysis. hGH-IBs present similar λmax intrinsic Trp fluorescence to the native protein (334 nm), indicative of a native-like tertiary structure. Similar fluorescence behavior was also obtained for hGH solubilized from IBs and native hGH at pH 10.0 and 2.5 kbar and after decompression. hGH-IBs expressed in E. coli were extracted to high yield and purity (95%) and solubilized using non-denaturing conditions [2.4 kbar, 0.25 M arginine (pH 10), 10 mM DTT]. After decompression, the protein was incubated at pH 7.4 in the presence of the glutathione-oxidized glutathione (GSH-GSSG) pair which led to intramolecular disulfide bond formation and refolded hGH (81% yield).

Conclusions

We have shown that hGH-IBs present native-like secondary and tertiary structures and that non-denaturing methods that aim to preserve them can lead to high yields of refolded protein. It is likely that the refolding process described can be extended to different proteins and may be particularly useful to reduce the pH required for alkaline solubilization.
Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study)
Authors: Valdés Sergio , Doulatram-Gamgaram Viyey , Maldonado-Araque Cristina , Lago-Sampedro Ana , García-Escobar Eva , García-Serrano Sara , García-Vivanco Marta , Garrido Juan Luis , Theobald Mark Richard , Gil Victoria , Martín-Llorente Fernando , Ocon Pilar , Calle-Pascual Alfonso , Castaño Luis , Delgado Elías , Menendez Edelmiro , Franch-Nadal Josep , Gaztambide Sonia , Girbés Joan , Chaves F Javier , Galán-García José L , Aguilera-Venegas Gabriel , Gutierrez-Repiso Carolina , Fernández-García José Carlos , Colomo Natalia , Soriguer Federico , García-Fuentes Eduardo , Rojo-Martínez Gemma
Published: August 2022

Background

Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain.

Methods

The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche).

Results

In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 μg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women.

Conclusions

Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.
Natural products: potential drugs for the treatment of renal fibrosis
Authors: Zhou Zijun , Qiao Yanheng , Zhao Yanru , Chen Xin , Li Jie , Zhang Hanqing , Lan Qiumei , Yang Bo
Published: August 2022

With the increasing prevalence and mortality, chronic kidney disease (CKD) has become a world public health problem. As the primary pathological manifestation in CKD, renal fibrosis is often used as a critical target for the treatment of CKD and inhibits the progression of CKD to end-stage renal disease (ESRD). As a potential drug, natural products have been confirmed to have the potential as a routine or supplementary therapy for chronic kidney disease, which may target renal fibrosis and act through various pharmacological activities such as anti-inflammatory and anti-oxidation of natural products. This article briefly introduces the pathological mechanism of renal fibrosis and systematically summarizes the latest research on the treatment of renal fibrosis with natural products of Chinese herbal medicines.
RETRACTED ARTICLE: The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA
Authors: Feng Zengyu , Li Kexian , Qin Kai , Liang Juyong , Shi Minmin , Ma Yang , Zhao Shiwei , Liang Huaiyu , Han Dongni , Shen Baiyong , Peng Chenghong , Chen Hao , Jiang Lingxi
Published: August 2022

Background

Although a substantial increase in the survival of patients with other cancers has been observed in recent decades, pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest diseases. No effective screening approach exists.

Methods

Differential exosomal long noncoding RNAs (lncRNAs) isolated from the serum of patients with PDAC and healthy individuals were profiled to screen for potential markers in liquid biopsies. The functions of LINC00623 in PDAC cell proliferation, migration and invasion were confirmed through in vivo and in vitro assays. RNA pulldown, RNA immunoprecipitation (RIP) and coimmunoprecipitation (Co-IP) assays and rescue experiments were performed to explore the molecular mechanisms of the LINC00623/NAT10 signaling axis in PDAC progression.

Results

A novel lncRNA, LINC00623, was identified, and its diagnostic value was confirmed, as it could discriminate patients with PDAC from patients with benign pancreatic neoplasms and healthy individuals. Moreover, LINC00623 was shown to promote the tumorigenicity and migratory capacity of PDAC cells in vitro and in vivo. Mechanistically, LINC00623 bound to N-acetyltransferase 10 (NAT10) and blocked its ubiquitination-dependent degradation by recruiting the deubiquitinase USP39. As a key regulator of N4-acetylcytidine (ac4C) modification of mRNA, NAT10 was demonstrated to maintain the stability of oncogenic mRNAs and promote their translation efficiency through ac4C modification.

Conclusions

Our data revealed the role of LINC00623/NAT10 signaling axis in PDAC progression, showing that it is a potential biomarker and therapeutic target for PDAC.
Clinical and cost-effectiveness of paramedic administered fascia iliaca compartment block for emergency hip fracture (RAPID 2)—protocol for an individually randomised parallel-group trial
Authors: Kingston Mark , Jones Jenna , Black Sarah , Evans Bridie , Ford Simon , Foster Theresa , Goodacre Steve , Jones Marie-Louise , Jones Sian , Keen Leigh , Longo Mirella , Lyons Ronan A. , Pallister Ian , Rees Nigel , Siriwardena Aloysius Niroshan , Watkins Alan , Williams Julia , Wilson Helen , Snooks Helen
Published: August 2022

Background

Approximately 75,000 people fracture a hip each year in the UK. This painful injury can be devastating—with a high associated mortality rate—and survivors likely to be more dependent and less mobile. Pain relief at the scene of injury is known to be inadequate. Intravenous morphine is usually given by paramedics, but opioids are less effective for dynamic pain and can cause serious side effects, including nausea, constipation, delirium and respiratory depression. These may delay surgery, require further treatment and worsen patient outcomes. We completed a feasibility study of paramedic-provided fascia iliaca compartment block (FICB), testing the intervention, trial methods and data collection. The study (RAPID) demonstrated that a full trial was feasible. In this subsequent study, we aim to test safety, clinical and cost-effectiveness of paramedic-provided FICB as pain relief to patients with suspected hip fracture in the prehospital environment.

Methods

We will conduct a pragmatic multi-centre individually randomised parallel-group trial, with a 1:1 allocation between usual care (control) and FICB (intervention). Hospital clinicians in five sites (paired ambulance services and receiving hospitals) in England and Wales will train 220 paramedics to administer FICB. The primary outcome is change in pain score from pre-randomisation to arrival at the emergency department. One thousand four hundred patients are required to find a clinically important difference between trial arms in the primary outcome (standardised statistical effect ~ 0.2; 90% power, 5% significance). We will use NHS Digital (England) and the SAIL (Secure Anonymised Information Linkage) databank (Wales) to follow up patient outcomes using routine anonymised linked data in an efficient study design, and questionnaires to capture patient-reported outcomes at 1 and 4 months. Secondary outcomes include mortality, length of hospital stay, job cycle time, prehospital medications including morphine, presence of hip fracture, satisfaction, mobility, and NHS costs. We will assess safety by monitoring serious adverse events (SAEs).

Discussion

The trial will help to determine whether paramedic administered FICB is a safe, clinically and cost-effective treatment for suspected hip fracture in the pre-hospital setting. Impact will be shown if and when clinical guidelines either recommend or reject the use of FICB in routine practice in this context.

Trial registration

ISRCTN15831813. Registered on 22 September 2021.
SHIFTPLAN: a randomized controlled trial investigating the effects of a multimodal shift-work intervention on drivers’ fatigue, sleep, health, and performance parameters.
Authors: Declercq Inge , Van Den Eede Filip , Roelant Ella , Verbraecken Johan
Published: August 2022

Background

Shift work is commonly associated with health problems resulting from circadian misalignment and sleep restriction. About one in three shift workers is affected by insomnia and up to 90% report regular fatigue and/or sleepiness at the workplace. Epidemiological data shows that shift workers are at increased risk of cardiovascular disease, diabetes, obesity, breast cancer, mental-health problems, and shift-work disorder, which conditions typically lead to reduced work performance, processing errors, accidents at work, absenteeism, and reduced quality of life. Given these widespread and debilitating consequences, there is an urgent need for treatments that help improve the sleep, health, and functional performance of the shift-working population. The most common non-pharmacological recommendations are improved scheduling, bright-light exposure, napping, psychoeducation promoting sleep hygiene, and cognitive-behavioral techniques. The objectives of the present study are to investigate the effects of a multimodal shift-work intervention on perceived fatigue, sleepiness, physical and mental health, sleep parameters, and absenteeism.

Methods

A randomized controlled interventional study comparing the two groups each comprising at least 80 drivers of a public transport company, using self-report questionnaires and health checks completed at intake and after 3 and 6 months following the start of the intervention or waiting-list period. The intervention consists of (a) healthy scheduling taking into account shift-rotation direction and speed, chronotype, resting time, and napping; (b) an education program specifically developed for shift workers; and (c) a dedicated information campaign for shift planners. The primary outcome is symptomatic burden in terms of sleepiness, and the key secondary outcome is symptomatic burden in terms of fatigue. Supplementary secondary outcomes are sleep parameters, absenteeism, general and clinical health, changes in mood, and anxiety.

Discussion

Expected outcomes are significant improvements on all primary and secondary outcome parameters in the intervention group. To our knowledge, ours is the first randomized controlled study to systematically investigate the effects of a multimodal program on multiple health, sleep, and performance parameters in shift workers. Our research also aims at providing evidence-based practice guidelines for healthy scheduling in general and thus contribute to diminishing the serious health and economic burdens associated with shift work overall.

Trial registration

EDGE registration number: 000339. ClinicalTrials.gov NCT05452096
Integrated traditional Chinese medicine intervention for delaying HIV morbidity: study protocol for a multicentre randomised controlled trial
Authors: Ding Xue , Meng Pengfei , Ma Xiuxia , Cui Weifeng , Li Liangping , Song Xiyuan , Wang Jiangrong , Ma Chengjie , Chen Xin , Xu Liran
Published: August 2022

Background

Acquired immune deficiency syndrome is caused by humans and is high worldwide. Active antiretroviral therapy emerged in the late 1990s and is effective against AIDS. However, despite the extensive research on AIDS, there is still no vaccine or cure. The benefits of traditional Chinese medicine (TCM) for AIDS are increasingly recognised, especially by patients with asymptomatic HIV infection.

Methods/design

The proposed trial will enrol 216 eligible patients who will be randomised into treatment and control groups. After 72 weeks of intervention, the efficacy and safety of TCM for patients with AIDS will be assessed. The variables that will be measured include clinical symptoms, TCM syndromes, viral load, immunological indicators, inflammatory factors, quality of life, patient-reported outcomes and safety assessment.

Discussion

The study aim to compare the effectiveness and safety of TCM for asymptomatic AIDS and explore its potential underlying mechanism. Additionally, the findings will provide a reference for the use of TCM to delay the onset and control the progression of HIV/AIDS.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800018365. Registered on 13 September 2018
Improved energy efficiency in microbial fuel cells by bioethanol and electricity co-generation
Authors: Xie Rong , Wang Shuang , Wang Kai , Wang Meng , Chen Biqiang , Wang Zheng , Tan Tianwei
Published: August 2022

Background

Microbial electricity production has received considerable attention from researchers due to its environmental friendliness and low price. The increase in the number of intracellular electrons in a microbial fuel cell (MFC) helps to improve the MFC performance.

Results

In this study, we accumulated excess electrons intracellularly by knocking out the gene related to intracellular electron consumption inSaccharomyces cerevisiae, and the elevated intracellular electron pool positively influenced the performances of MFCs in terms of electricity production, while helping to increase ethanol production and achieve ethanol and electricity co-production, which in turn improved the utilization of substrates. The final knockout strain reached a maximum ethanol yield of 7.71 g/L and a maximum power density of 240 mW/m2in the MFC, which was 12 times higher than that of the control bacteria, with a 17.3% increase in energy utilization.

Conclusions

The knockdown of intracellular electron-consuming genes reported here allowed the accumulation of excess electrons in cells, and the elevated intracellular electron pool positively influenced the electrical production performance of the MFC. Furthermore, by knocking out the intracellular metabolic pathway, the yield of ethanol could be increased, and co-production of ethanol and electricity could be achieved. Thus, the MFC improved the utilization of the substrate.
High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses
Authors: Heming Michael , Börsch Anna-Lena , Wiendl Heinz , Meyer zu Hörste Gerd
Published: August 2022

The cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were identified as a neuroimmunological interface, highlighting the potential of exploring central nervous system (CNS) immunity by studying CNS border compartments. Here, we summarize how single-cell transcriptomics of such border compartments advance our understanding of neurological diseases, the challenges that remain, and what opportunities novel multi-omic methods offer. Single-cell transcriptomics studies have detected cytotoxic CD4+ T cells and clonally expanded T and B cells in the CSF in the autoimmune disease multiple sclerosis; clonally expanded pathogenic CD8+ T cells were found in the CSF and in the brain adjacent to β-amyloid plaques of dementia patients; in patients with brain metastases, CD8+ T cell clonotypes were shared between the brain parenchyma and the CSF and persisted after therapy. We also outline how novel multi-omic approaches permit the simultaneous measurements of gene expression, chromatin accessibility, and protein in the same cells, which remain to be explored in the CSF. This calls for multicenter initiatives to create single-cell atlases, posing challenges in integrating patients and modalities across centers. While high-dimensional analyses of CSF cells are challenging, they hold potential for personalized medicine by better resolving heterogeneous diseases and stratifying patients.
Multi-nuclear magnetic resonance spectroscopy: state of the art and future directions
Authors: Wei Yi , Yang Caiwei , Jiang Hanyu , Li Qian , Che Feng , Wan Shang , Yao Shan , Gao Feifei , Zhang Tong , Wang Jiazheng , Song Bin
Published: August 2022

With the development of heteronuclear fluorine, sodium, phosphorus, and other probes and imaging technologies as well as the optimization of magnetic resonance imaging (MRI) equipment and sequences, multi-nuclear magnetic resonance (multi-NMR) has enabled localize molecular activities in vivo that are central to a variety of diseases, including cardiovascular disease, neurodegenerative pathologies, metabolic diseases, kidney, and tumor, to shift from the traditional morphological imaging to the molecular imaging, precision diagnosis, and treatment mode. However, due to the low natural abundance and low gyromagnetic ratios, the clinical application of multi-NMR has been hampered. Several techniques have been developed to amplify the NMR sensitivity such as the dynamic nuclear polarization, spin-exchange optical pumping, and brute-force polarization. Meanwhile, a wide range of nuclei can be hyperpolarized, such as2H,3He,13C,15 N,31P, and129Xe. The signal can be increased and allows real-time observation of biological perfusion, metabolite transport, and metabolic reactions in vivo, overcoming the disadvantages of conventional magnetic resonance of low sensitivity. HP-NMR imaging of different nuclear substrates provides a unique opportunity and invention to map the metabolic changes in various organs without invasive procedures. This review aims to focus on the recent applications of multi-NMR technology not only in a range of preliminary animal experiments but also in various disease spectrum in human. Furthermore, we will discuss the future challenges and opportunities of this multi-NMR from a clinical perspective, in the hope of truly bridging the gap between cutting-edge molecular biology and clinical applications.
Successful treatment with daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report
Authors: Taenaka Ryutaro , Shimokawa Sakurako , Katayama Ayako , Nagao Toshihiko , Obara Teppei , Nishimura Naoaki , Tsujimoto Atsushi , Kohno Kentaro , Aoki Kenichi , Ogawa Ryosuke
Published: August 2022

Background

Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients.

Case presentation

A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared.

Conclusions

Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.
Black-box adversarial attacks through speech distortion for speech emotion recognition
Authors: Gao Jinxing , Yan Diqun , Dong Mingyu
Published: August 2022

Speech emotion recognition is a key branch of affective computing. Nowadays, it is common to detect emotional diseases through speech emotion recognition. Various detection methods of emotion recognition, such as LTSM, GCN, and CNN, show excellent performance. However, due to the robustness of the model, the recognition results of the above models will have a large deviation. So in this article, we use black boxes to combat sample attacks to explore the robustness of the model. After using three different black-box attacks, the accuracy of the CNN-MAA model decreased by 69.38% at the best attack scenario, while the word error rate (WER) of voice decreased by only 6.24%, indicating that the robustness of the model does not perform well under our black-box attack method. After adversarial training, the model accuracy only decreased by 13.48%, which shows the effectiveness of adversarial training against sample attacks. Our code is available in Github.
Association between mother’s work status and child stunting in urban slums: a cross-sectional assessment of 346 child-mother dyads in Dhaka, Bangladesh (2020)
Authors: Win Hayman , Shafique Sohana , Mizan Sharmin , Wallenborn Jordyn , Probst-Hensch Nicole , Fink Günther
Published: August 2022

Background

A growing literature highlights the increased risk of stunting among children growing up in informal or slum settlements. Despite relatively high rates of female labor force participation in slums, there is limited evidence on relationship between mother’s work participation and nutritional outcomes of children in these settings.

Methods

We conducted a cross-sectional study in two large slums (Korail and Tongi) of Dhaka and Gazipur, Bangladesh to assess the association between maternal work and childhood stunting in a low-income urban context. Logistic regression models estimated unconditional and conditional associations between maternal work status and 1) child stunting, 2) child morbidity and dietary intake, and 3) health and hygiene behaviors. Subgroup analyses were done by type of child care support available.

Results

After adjusting for variations in individual and household level characteristics, we found that children of working mothers had nearly twice the odds of being stunted than children of non-working mothers (OR 1.84, 95%CI 1.05-3.23). Large differences in stunting were found by available care support: compared to children of non-working mothers, children of working mothers with nuclear-type family support had 4.5 times increased odds of stunting (OR 4.49, 95%CI 1.81-11.12), while no odds differential was found for children of working mothers with an extended-type family support (OR 0.69, 95%CI 0.30-1.59).

Conclusions

Maternal employment is associated with a substantial increase in the odds of child stunting in the slum areas studied. Given that these effects only appear to arise in the absence of adequate family support, integrating appropriate childcare support measures for low-income urban working mothers might be an effective strategy to help reduce the prevalence of chronic undernutrition among slum children.
A proposal for virtual, telephone-based preoperative cognitive assessment in older adults undergoing elective surgery
Authors: Cooper Lisa , Krishnan Sindhu , Javedan Houman , Bader Angela M. , Tulabaev Samir
Published: August 2022

Objective

To assess the feasibility of administering the MoCA 5-minute test/Telephone (T-MoCA), an abbreviated version of the Montreal Cognitive Assessment to older adults perioperatively

Design

A feasibility study including patients aged ≥ 70 years scheduled for surgery from December 2020 to March 2021

Setting

Preoperative virtual clinic

Patients

Patients ≥70 years undergoing major elective surgery

Intervention

A study investigator called eligible patients prior to surgery, obtained consent, and completed the preoperative cognitive assessment. Follow-up assessment was completed 1-month postoperatively, and participating clinicians were surveyed at the completion of the study.

Measurements

An attention test, T-MoCA, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and Generalized Anxiety Disorder 2-item (GAD-2)

Main results

Overall, 37/40 (92.5%) patients completed the pre- and post-operative assessments. The cohort was 50% female, white (97.5%), with a median age of 76 years (interquartile range (IQR) 73-79), and education level was higher than high school in 82.5% of patients. Preoperatively, the median number of medications was 8 (IQR 7-11), 27/40 (67.5%) had medications with anticholinergic effects, and 6/40 (15%) had benzodiazepines. Median completion time of the phone assessment was 10 min (IQR 8.25-12) and 4 min (IQR 3-5) for the T-MoCA with a median T-MoCA score of 13 (IQR 12-14). Most patients (37/40) completed the post-operative assessment, and 6/37 (16.2%) reported they had experienced a change in memory or attention post-operatively. Clinician’s survey reported ease and feasibility in performing T-MoCA as a preoperative cognitive evaluation.

Conclusion

Preoperative cognitive assessment of older adults using T-MoCA over the phone is easy to perform by clinicians and had a high completion rate by patients. This test is feasible for virtual assessments. Further research is needed to better define validity and correlation with postoperative outcomes.
Antimicrobial susceptibility testing of Staphylococcus aureus isolates from patients at a tertiary hospital in Tehran, Iran, 2018–2019
Authors: Qodrati Mohammad , SeyedAlinaghi SeyedAhmad , Dehghan Manshadi Seyed Ali , Abdollahi Alireza , Dadras Omid
Published: August 2022

Background

Staphylococcus aureus, a human skin and mucous membranes colonizer, could opportunistically cause a variety of infectious diseases. Frequently, it is resistant to methicillin (MRSA), and often, co-resistant to many clinically available antibiotics. MRSA is a major burden for healthcare systems and communities all over the world, especially in developing countries. We addressed the issue that more than a decade had passed since the last report about cumulative antibiogram for S. aureus from our center, whereas The Clinical and Laboratory Standards Institute (CLSI) recommends to analyze and report it on an annual basis in order to guide clinicians to select the best initial empiric antimicrobial therapy.

Methods

In a cross-sectional retrospective design, data of culture-proven S. aureus from clinical specimens of hospitalized patients at Imam Khomeini Hospital Complex, Tehran, Iran, were collected from September 2018 to September 2019. Antimicrobial susceptibility testing (AST) had been performed using either Kirby–Bauer disk diffusion or VITEK 2 automated system which is based on minimum inhibitory concentration (MIC). The Chi-squared test was used considering the critical p-value to be ≤ .05.

Results

Among 576 unique isolates, the overall prevalence of MRSA was 37.5%. Patients admitted to the infectious diseases ward and ICUs have a greater chance to have such an isolate. Methicillin resistance was predictive of resistance to most antibiotics: erythromycin (90.9%), clindamycin (85.4% including inducible resistance), gentamicin, cipro-/levo-/moxi-floxacin, trimethoprim–sulfamethoxazole (58.3%), tetracycline, and rifampin. Resistance rate of zero was observed for daptomycin, linezolid, tigecycline, and (roughly) vancomycin. The prevalence of multiple-drug resistant (MDR) isolates was 48.5%.

Conclusions

Although in this study, the prevalence of MRSA was lower than the previous ones from the same hospital, it is still far from the desired rates. Besides, resistance to clindamycin and trimethoprim–sulfamethoxazole were remarkable. So far, vancomycin is the best choice for empiric treatment of MRSA, with linezolid as the second choice. It is advised to avoid prescribing the newer antibacterial agents as long as the older ones are effective to prevent the emergence of MDR species.
Comparative genomic analysis of five freshwater cyanophages and reference-guided metagenomic data mining
Authors: Du Kang , Yang Feng , Zhang Jun-Tao , Yu Rong-Cheng , Deng Ziqing , Li Wei-Fang , Chen Yuxing , Li Qiong , Zhou Cong-Zhao
Published: August 2022

Background

As important producers using photosynthesis on Earth, cyanobacteria contribute to the oxygenation of atmosphere and the primary production of biosphere. However, due to the eutrophication of urban waterbodies and global warming, uncontrollable growth of cyanobacteria usually leads to the seasonal outbreak of cyanobacterial blooms. Cyanophages, a group of viruses that specifically infect and lyse cyanobacteria, are considered as potential environment-friendly agents to control the harmful blooms. Compared to the marine counterparts, only a few freshwater cyanophages have been isolated and genome sequenced to date, largely limiting their characterizations and applications.

Results

Here, we isolated five freshwater cyanophages varying in tail morphology, termed Pam1~Pam5, all of which infect the cyanobacterium Pseudanabaena mucicola Chao 1806 that was isolated from the bloom-suffering Lake Chaohu in Anhui, China. The whole-genome sequencing showed that cyanophages Pam1~Pam5 all contain a dsDNA genome, varying in size from 36 to 142 Kb. Phylogenetic analyses suggested that Pam1~Pam5 possess different DNA packaging mechanisms and are evolutionarily distinct from each other. Notably, Pam1 and Pam5 have lysogeny-associated gene clusters, whereas Pam2 possesses 9 punctuated DNA segments identical to the CRISPR spacers in the host genome. Metagenomic data-based calculation of the relative abundance of Pam1~Pam5 at the Nanfei estuary towards the Lake Chaohu revealed that the short-tailed Pam1 and Pam5 account for the majority of the five cyanophages. Moreover, comparative analyses of the reference genomes of Pam1~Pam5 and previously reported cyanophages enabled us to identify three circular and seven linear contigs of virtual freshwater cyanophages from the metagenomic data of the Lake Chaohu.

Conclusions

We propose a high-throughput strategy to systematically identify cyanophages based on the currently available metagenomic data and the very limited reference genomes of experimentally isolated cyanophages. This strategy could be applied to mine the complete or partial genomes of unculturable bacteriophages and viruses. Transformation of the synthesized whole genomes of these virtual phages/viruses to proper hosts will enable the rescue of bona fide viral particles and eventually enrich the library of microorganisms that exist on Earth.
Spatial distribution of insecticide resistant populations of Aedes aegypti and Ae. albopictus and first detection of V410L mutation in Ae. aegypti from Cameroon
Authors: Montgomery Matthew , Harwood James F. , Yougang Aurelie P. , Wilson-Bahun Theodel A. , Tedjou Armel N. , Keumeni Christophe Rostand , Kilpatrick Auston Marm , Wondji Charles S. , Kamgang Basile
Published: August 2022

Background

Dengue (DENV), chikungunya (CHIKV) and Zika virus (ZIKV), are mosquito-borne viruses of medical importance in most tropical and subtropical regions. Vector control, primarily through insecticides, remains the primary method to prevent their transmission. Here, we evaluated insecticide resistance profiles and identified important underlying resistance mechanisms in populations of Aedes aegypti and Ae. albopictus from six different regions in Cameroon to pesticides commonly used during military and civilian public health vector control operations.

Methods

Aedes mosquitoes were sampled as larvae or pupae between August 2020 and July 2021 in six locations across Cameroon and reared until the next generation, G1. Ae. aegypti and Ae. albopictus adults from G1 were tested following World Health Organization (WHO) recommendations and Ae. aegypti G0 adults screened with real time melting curve qPCR analyses to genotype the F1534C, V1016I and V410L Aedes kdr mutations. Piperonyl butoxide (PBO) assays and real time qPCR were carried out from some cytochrome p450 genes known to be involved in metabolic resistance. Statistical analyses were performed using Chi-square test and generalized linear models.

Results

Loss of susceptibility was observed to all insecticides tested. Mortality rates from tests with 0.25% permethrin varied from 24.27 to 85.89% in Ae. aegypti and from 17.35% to 68.08% in Ae. albopictus. Mortality rates for 0.03% deltamethrin were between 23.30% and 88.20% in Ae. aegypti and between 69.47 and 84.11% in Ae. albopictus. We found a moderate level of resistance against bendiocarb, with mortality rates ranging from 69.31% to 90.26% in Ae. aegypti and from 86.75 to 98.95% in Ae. albopictus. With PBO pre-exposure, we found partial or fully restored susceptibility to pyrethroids and bendiocarb. The genes Cyp9M6F88/87 and Cyp9J10 were overexpressed in Ae. aegypti populations from Douala sites resistant to permethrin and deltamethrin. Cyp6P12 was highly expressed in alphacypermethrin and permethrin resistant Ae. albopictus samples. F1534C and V1016I mutations were detected in A. aegypti mosquitoes and for the first time V410L was reported in Cameroon.

Conclusions

This study revealed that Ae. aegypti and Ae. albopictus are resistant to multiple insecticide classes with multiple resistance mechanisms implicated. These findings could guide insecticide use to control arbovirus vectors in Cameroon.
Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease
Authors: Gelpi Ellen , Baiardi Simone , Nos Carlos , Dellavalle Sofia , Aldecoa Iban , Ruiz-Garcia Raquel , Ispierto Lourdes , Escudero Domingo , Casado Virgina , Barranco Elena , Boltes Anuncia , Molina-Porcel Laura , Bargalló Nuria , Rossi Marcello , Mammana Angela , Tiple Dorina , Vaianella Luana , Stoegmann Elisabeth , Simonitsch-Klupp Ingrid , Kasprian Gregor , Klotz Sigrid , Höftberger Romana , Budka Herbert , Kovacs Gabor G. , Ferrer Isidre , Capellari Sabina , Sanchez-Valle Raquel , Parchi Piero
Published: August 2022

The methionine (M)—valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.
C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease
Authors: Gomez-Arboledas Angela , Carvalho Klebea , Balderrama-Gutierrez Gabriela , Chu Shu-Hui , Liang Heidi Yahan , Schartz Nicole D. , Selvan Purnika , Petrisko Tiffany J. , Pan Miranda A. , Mortazavi Ali , Tenner Andrea J.
Published: August 2022

Multiple studies have recognized the involvement of the complement cascade during Alzheimer’s disease pathogenesis. However, the specific role of C5a-C5aR1 signaling in the progression of this neurodegenerative disease is still not clear. Furthermore, its potential as a therapeutic target to treat AD still remains to be elucidated. Canonically, generation of the anaphylatoxin C5a as the result of complement activation and interaction with its receptor C5aR1 triggers a potent inflammatory response. Previously, genetic ablation of C5aR1 in a mouse model of Alzheimer’s disease exerted a protective effect by preventing cognitive deficits. Here, using PMX205, a potent, specific C5aR1 antagonist, in the Tg2576 mouse model of Alzheimer’s disease we show a striking reduction in dystrophic neurites in parallel with the reduced amyloid load, rescue of the excessive pre-synaptic loss associated with AD cognitive impairment and the polarization of microglial gene expression towards a DAM-like phenotype that are consistent with the neuroprotective effects seen. These data support the beneficial effect of a pharmacological inhibition of C5aR1 as a promising therapeutic approach to treat Alzheimer’s disease. Supportive of the safety of this treatment is the recent FDA-approval of another other C5a receptor 1 antagonist, Avacopan, as a treatment for autoimmune inflammatory diseases.