bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Air-Sea Coupling on November-April Intraseasonal Rainfall Variability Over the South Pacific
Authors: Pariyar Sunil Kumar , Keenlyside Noel , Tseng Wan-Ling , Hsu Huang Hsiung , Tsuang Ben-jei
Published: September 2021

We investigate the impact of resolving air-sea interaction on the simulation of the intraseasonal rainfall variability over the South Pacific using the ECHAM5 atmospheric general circulation model coupled with the Snow-Ice-Thermocline (SIT) ocean model. We compare the fully coupled simulation with two uncoupled ECHAM5 simulations, one forced with sea surface temperature (SST) climatology and one forced with daily SST from the coupled model. The intraseasonal rainfall variability over the South Pacific is reduced by 17% in the uncoupled model forced with SST climatology and increased by 8% in the uncoupled simulation forced with daily SST, suggesting the role of air-sea coupling and SST variability. The coupled model best simulates the key characteristics of two intraseasonal rainfall modes over the South Pacific with reasonable propagation and correct periodicity. The spatial structure of the two rainfall modes in all three simulations is very similar, suggesting these modes are primarily generated by the dynamics of the atmosphere. The southeastward propagation of rainfall anomalies associated with two leading rainfall modes in the South Pacific depends upon the eastward propagating MJO signals over the Indian Ocean and western Pacific. Air-sea interaction seems crucial for such propagation as both eastward and southeastward propagations are substantially reduced in the uncoupled model forced with SST climatology. The simulation of both eastward and southeastward propagations improved considerably in the uncoupled model forced with daily SST; however, the periodicity differs from the coupled model. Such discrepancy in the periodicity is attributed to the changes in the SST-rainfall relationship with weaker correlations and the nearly in-phase relationship.
Milk and Meat Consumption Patterns and the Potential Risk of Zoonotic Disease Transmission among Urban and Peri-urban Dairy Farmers in Ethiopia
Authors: Deneke Tilaye Teklewold , Bekele Adam , Moore Henrietta L. , Mamo Tadele , Almaw Gizat , Mekonnen Getnet Abie , Mihret Adane , Tschopp Rea , Yeheyis Likawent , Hodge Catherine , Wood James L.N. , Berg Stefan , consortium the ETHICOBOTS
Published: September 2021

Background: In the Ethiopian dairy farming system, prevalence of zoonotic diseases such as bovine tuberculosis (bTB) is high in the cattle population. This, combined with some risky milk and meat consumption habits, such as raw milk and uninspected raw meat consumption, poses a considerable risk of zoonotic disease transmission. A survey was conducted to investigate milk and meat consumption patterns, and the level of exposure to urban and peri-urban dairy-keeping households for risks of zoonotic disease transmission.Methods: Data on milk and meat consumption behaviours and other socioeconomic and demographic variables were collected from 480 urban and peri-urban dairy farms randomly surveyed in major towns in Ethiopia (Mekele, Hawassa, and Gondar towns, Addis Ababa city, as well as five Oromia towns around Addis Ababa). Determinants of raw milk consumption associated with a number of demographic and socio-economic factors were analysed using a generalized ordered logistic model.Results: The results indicated that about 20% the population consumed raw milk and their awareness about pasteurization and its benefits were low. Location, gender of the household head, previous bTB testing of cattle on the farm, knowledge of zoonotic risks associated with raw milk consumption, household size, and per-capita milk consumption were found to be important determinants of the frequency of raw milk consumption. About 60% of the respondents were exposed to the risk of zoonotic diseases through their habit of frequently consuming raw meat. This was depite that over 90% of the respondants were aware of possible zoonotic risks of raw meat consumption. The determinants of raw meat consumption behaviours were associated with location, gender and age of the household head, household size, meat type preference, per-capita meat consumption, knowledge about disease transmission risks, and training on zoonoses. Conclusion: Creating awareness about the risk factors for zoonotic transmission of diseases including bTB through training and media campaigns, improving meat hygiene through better abattoir services, and inducing behavioural change around meat sourcing, raw meat and raw milk consumption, are all crucial to the successful prevention and control of the spread of zoonotic diseases, including bTB.
An Association of Quality of Life and Ageing Perceptions Among Community Dwelling Older Adults in Uganda
Authors: -Onoria Joy Louise , Odokonyero Raymond , Giordani Bruno , Akena Dickens , Mwesiga Emmanuel , Ssuna Bashir , Ray Stuart C. , Bollinger Robert C. , Sewankambo Nelson K. , Nakasujja Noeline
Published: September 2021

Background: Uganda’s population, though, largely characterized by young people, has seen the number of people aged 60 and over grow from 686,000 twenty years ago, to 1,433,596 in 2014. Effective caring for the well-being of this population requires strategic and deliberate planning that involves quality of life (QoL) assessments. QoL assessments among the elderly are important in evaluating the efficacy of strategies, such as health interventions, welfare programs, health care, and well-being of the elderly. However, elderly in Uganda face several challenges, ranging from loneliness, poor housing, lack of social and financial support, and poor health. These may negatively affect older persons’ quality of life and consequently their perceptions and attitudes towards aging. Methods: The study was carried out in 2019 in the communities of Nansana and Busukuma town councils in Wakiso district, Uganda. The participants were 380 people 60 years and older. To establish the association between perceptions of ageing and QoL, this study utilized a locally adapted version of the Older Person’s Quality of Life Questionnaire (OPQOL) and the Brief Ageing Perceptions Questionnaire (B-APQ). The OPQOL assesses three domains of QoL: Health QoL (HQoL); Social economic QoL (SQoL); and Psychosocial QoL (PQoL). The B-APQ assesses perceptions about physical age, participation in social activities, and perceptions about ability to regulate emotions as one ages. Pearson’s Chi-square tests were used to characterize the relationship between the perceptions and quality of life.Results: The majority of the respondents, 61% (95%CI 56.7-64.8), had negative perceptions towards ageing. Eighty six percent had poor HQoL, 90% poor SQoL and 83% poor PQoL. There was a significant association between good HQoL and positive perception about participation in social activities (X2 = 7.3670, P = 0.007) as well as with positive perception on regulation of emotions (X2 = 18.1803, P<0.001). There was a significant association between good SQoL and positive perception about participation in social activities (X2 = 5.3472, P = 0.021), as well with positive perception on regulation of emotions (X2 = 10.5128, P<0.001). A significant association between good PQoL and positive perception on regulation of emotions (X2 = 9.2414, P= 0.002).Conclusion: Positive perceptions of ageing are associated with good QoL. Directly addressing perceptions of ageing could be a low cost and effective strategy to improve the QoL of older persons in SSA
Pulse-picking coherent anti-Stokes Raman scattering microscopy for highly sensitive chemical imaging
Authors: Clark Matthew , Gonzalez Gil , Zhang Chi
Published: September 2021

Coherent Raman scattering has been developed into powerful technologies for the chemical imaging of biological samples. However, limited sensitivity remains a critical bottleneck for coherent Raman microscopes. We introduce a pulse-picking technology that can significantly increase the sensitivity of coherent anti-Stokes Raman scattering (CARS) microscopy. An acousto-optic modulator driven by a function generator allows picking collinearly combined pump and Stokes pulses at low duty cycles. This method reduces the number of pulses at each image pixel, enhances the peak power of laser pulses, and thus significantly improves the sensitivity of CARS and minimizes phototoxicity. We demonstrated an over 1000-fold sensitivity improvement for CARS imaging. Besides, we show this pulse-picking method can enhance the sensitivity of multiphoton fluorescence and second harmonic generation modalities about 20 times. Using cell and biological tissue samples, we highlight the potential of this pulse-picking technology for highly sensitive multimodal chemical imaging in biological and medical sciences.
Is the Femoral Component Flexion Affected by the Sagittal Femoral Shaft Bowing in Conventional Intramedually Guided TKA?
Authors: Zhang Xiaofeng , Wang Qianjin , Xu Xingquan , Chen Dongyang , Bao Zhengyuan , Yao Yao , Wu Dengxian , Wang Bin , Xu Zhihong , Jiang Qing
Published: September 2021

Background: The aim of the present study was to investigate the influence of sagittal femoral bowing on sagittal femoral component alignment, and whether there was correlation between sagittal femoral component alignment and coronal femoral component alignment.Methods: We retrospectively reviewed 77 knees in 71 patients who had undergone primary TKA for advanced osteoarthritis.All surgeries were performed by using a standard medial parapatellar approach. The osteotomy was performed with a conventional technique using an intramedullar rod for the femur and a mechanical extramedullar guiding system for the tibia. All patients enrolled in the study were evaluated with full-length lower extremity load-bearing standing scanograms and the patients had preoperative and postoperative radiographs of the knees. cFBA(coronal femoral bowing angle), sFBA(sagittal femoral bowing angle),and postoperatively, mTFA(mechanical tibiofemoral angle of the knee), β angle(femoral component flexion angle) were measured. The radiographic results of both groups were compared using Student's t test. A two-sided Pearson correlation coefficient was obtained to identify the correlations between FBA in the coronal and sagittal planes, as well as FBA and age or BMI, sFBA and β angle, cFBA and mTFA. Comparison of FSB incidence between different genders was using chi-square test. The p value <0.05 indicates a statistically significant difference.Results: The mean sFBA, cFBA, β angle, mTFA were 9.34°±3.56°(range 1°-16°), 3.25°±3.79°(range -7°-17°), 3.91°±3.15°(range -1°-13°), 0.60°±1.95°(range -3°-6°), respectively. There was no correlation between age and sFBA(CC=0.192, p=0.194) or cFBA(CC=0.192, p=0.194), similarly, there was no correlation between age and sFBA(CC=0.067, p=0.565) or cFBA(CC=0.069, p=0.549). The sFBA was correlated with cFBA and β angle(CC=0.540, p<0.01; CC=0.543, p<0.01; respectively) and the cFBA was correlated with mTFA(CC=0.430, p<0.01). There was no significant difference(p=0.247) of cFBA between the patients with sFSB and the patients without sFSB. Conclusions: The current study showed that the sFBA was correlated with cFBA in the patients undergoing TKA and the patients with sFSB usually presented non-cFSB. We also found that sFSB could affect the femoral component alignment in the sagittal plane and cFSB could affect the femoral component alignment in the coronal plane. The sFBA or cFBA was not correlated with age, BMI or gender.
Anatomy of the Greater Occipital Nerve: Implications in Posterior Fossa Approaches.
Authors: LAINE Gaetan , JECKO Vincent , WAVASSEUR Thomas , GIMBERT Edouard , VIGNES Jean Rodolphe , LIGUORO Dominique
Published: September 2021

Purpose: Because of its superficial location in the dorsal regions of the scalp, the greater occipital nerve (GON) can be injured during neurosurgical procedures, resulting in post-operative pain and postural disturbances. The aim of this work is to specify the course of the GON and how its injuries can be avoided while performing posterior fossa approaches.Methods: This study was carried out at the department of anatomy in Bordeaux University. 4 specimens were dissected to study the GON course. Posterior fossa approaches (midline suboccipital, paramedian suboccipital, retrosigmoid and petrosal) were performed on 4 other specimens in order to assess potential risks of GON injuries.Results: The GON runs around the obliquus capitis inferior (100%), crosses the semispinalis capitis (100%) and the trapezius (75%) or its aponeurosis (25%). Direct GON injuries can be seen in paramedian suboccipital approaches. Stretching of the GON can occur in midline suboccipital and paramedian suboccipital approaches. We found no evidence of direct or indirect GON injury in retrosigmoid or petrosal approaches.Conclusion: Our study provides interesting data regarding the risk GON injury in posterior fossa approaches. Direct GON injuries in paramedian suboccipital approaches can be avoided with careful dissection. Placing retractors in contact with the periosteum and performing a minimal retraction may help to avoid excessive GON stretching in midline suboccipital and paramedian suboccipital approaches. Furthermore, incision for retrosigmoid approaches should be as lateral as possible and not too caudal. Finally, avoiding extreme patient positioning reduces the risk of GON stretching in all approaches.
Spatiotemporal Prediction of the Occurrence of Vancomycin-resistant Enterococcus
Authors: Niekerk J. M. van , Lokate M. , Braakman-Jansen L. M. A. , Gemert-Pijnen J. E. W. C. van , Stein A.
Published: September 2021

Background: Vancomycin-resistant enterococci (VRE) is the cause of severe patient health and monetary burdens. Antibiotic use is a confounding effect to predict VRE in patients, but the antibiotic use of patients who may have frequented the same ward as the patient in question is often neglected. This study investigated how the occurrence and spread of VRE can be explained by patient movements between hospital wards and their antibiotic use.Methods: Intrahospital patient movements, antibiotic use and PCR screening data were used from a hospital in the Netherlands. The PageRank algorithm was used to calculate two daily centrality measures based on the spatiotemporal graph to summarise the flow of patients and antibiotics at the ward level. A decision tree model was used to determine a simple set of rules to estimate the daily probability of VRE occurrence for each hospital ward. The model performance was improved using a random forest model and compared using 30% test sample.Results: Centrality covariates summarising the flow of patients and their antibiotic use between hospital wards can be used to predict the daily occurrence of VRE at the hospital ward level. The decision tree model produced a simple set of rules that can be used to determine the daily probability of VRE occurrence for each hospital ward. An acceptable area under the ROC curve (AUC) of 0.755 was achieved using the decision tree model and an excellent AUC of 0.883 by the random forest model on the test set. These results confirms that the random forest model performs better than a single decision tree for all levels of model sensitivity and specificity on data not used to estimate the models.Conclusion: This study showed how the movements of patients inside hospitals and their use of antibiotics could predict VRE occurrence at the ward level. Two daily centrality measures were proposed to summarise the flow of patients and antibiotics at the ward level. An early warning system for VRE can be developed to test and further develop infection prevention plans and outbreak strategies using these results.
Knockdown of microRNA-126 Suppresses Non-Small-Cell Lung Cancer via Inhibiting PI3K-AKT-mTOR Pathway
Authors: Chen Panfeng , Jiang Ping , Yu Xi , Yang Min
Published: September 2021

Background

As one of the most common cause of cancer death in the world, lung cancer causes approximate 1.6 million deaths annually. Among, NSCLC accounts approximately 85% of patients in whole lung cancer patients. As one of miRNAs, miR-126 closely involves in pathogenesis of several types of cancers including colorectal, prostate, bladder and gastric cancer, and so on. Thus, the present study aims to investigate effects of miR126 on pathogenesis of NSCLC. In the study, two lung cancer cell lines including A549 and H1650 were used.
Results

It was found that expression of miR126 was decreased in PBMC of NSCLC patients compared to healthy control. Expression of miR126 was decreased in cancer tissue compared to paracancerous tissues in NSCLC patients. MiR-126 KD remarkably increased expression of apoptosis genes including caspase3 and capsae9, and decreased cell viability in lung cancer cells including A549 and H1650 cells. Interesting, In Silico analysis indicated that miR-126 could target PI3K signaling pathway, which was confirmed by WB assay. KD of PI3KR2 compromised promotion of miR-126 on cell apoptosis. Similarly, it was found that KD of mTOR compromised promotion of miR-126 on cell apoptosis.
Conclusions

Thus, the present study confirmed that miR-126 plays an important role in apoptosis of lung cells via mTOR signaling pathway. miR-126 might be a potential therapeutic target for developing novel drugs against NSCLC.
Feasibility Analysis and Advantages of Wedge Resection Plus Transverse Suture Applied to Closure of Loop Ileostomy
Authors: Qin Hai-Quan , Liao Jian-Kun , Wang Wen-Tao , Meng Ling-Hou , Huang Zi-Gao , Mo Xian-Wei
Published: September 2021

Objectives: To evaluate the feasibility and advantages of wedge resection plus transverse suture applied to loop ileostomy closure by analyzing the surgical data and the incidence of postoperative complications of patients undergoing this procedure.Methods: We performed a retrospective analysis of the hospitalization data of patients who underwent ileostomy closure surgery and met the research standards from January 2017 to April 2021 in the Guangxi Medical University Cancer Hospital; all surgeries were performed by the same surgeon. The perioperative data were statistically analyzed by grouping.Results: In total, 65 patients were enrolled in this study, with 12 in the wedge resection group, 35 in the stapler group, and 18 in the hand suture group. There was no significant difference in operation time between the wedge resection group and stapler group (P > 0.05), but both groups had shorter operation time than that in the hand suture group (P< 0.05). The postoperative exhaustion time of wedge resection group was earlier than that of the others, and cost of surgical consumables in the wedge resection group was significantly lower than that in the stapler group, all with statistically significant differences (P< 0.05). By contrast, there was no statistically significant difference in postoperative complication incidences among the three groups.Conclusions: The wedge resection plus transverse suture is safe and easy for closure of loop ileostomy, and the intestinal motility recovers rapidly postoperatively. It has less surgical consumables, and is particularly suitable for the currently implemented Diagnosis-Related Groups payment method.
One Hundred Children and Adolescents Consulting General Practice With Musculoskeletal Pain.
Authors: Pourbordbari Negar , Jensen Martin Bach , Olesen Jens Lykkegaard , Holden Sinead , Rathleff Michael Skovdal
Published: September 2021

BackgroundEach year, 8% of all child and adolescent consultations in general practice are due to musculoskeletal conditions, with pain as the most frequent symptom. Despite the commonality of musculoskeletal pain, limited knowledge exists about care-seeking children and adolescents with musculoskeletal pain. The purpose of this study was to describe characteristics of children and adolescents consulting their general practitioner with musculoskeletal pain.MethodsThis is a cross-sectional study based on the baseline data from the child and adolescent musculoskeletal (ChiBPS) pain cohort study, carried out in 17 Danish general practice clinics. Patients aged 8-19 years with musculoskeletal pain complaints when consulting their GP completed a questionnaire on demographics, physical activity, pain impact, psychosocial factors, and expectations of their general practitioner. Descriptive statistics were used to summarize data. Normally distributed continuous data are described using mean and standard deviations while non-normally data are described using median and interquartile range. ResultsWe included 100 participants (54% female, median age 13 [12-16] years). The most frequent activity limiting pain regions were knee (56%), back (20%), ankle (19%), and neck (13%). The majority (63%) consulted their general practitioner because they were not able to use their body as usual due to pain. At time of consultation the median pain duration was 5 months [3 weeks-1 year]. Above a third were often or sometimes nervous (34%), worried or anxious (33%), and took pain medication when in pain (33%). Pain made it difficult to participate in sport activities at school (79%) and disturbed spare time activities (88%). Pain made it difficult to concentrate (58%) and to fall asleep (38%) and only 38% expected a pain free long-term future.ConclusionThis study demonstrates the bio-psycho-social impact of musculoskeletal pain in care-seeking children and adolescents. Demographics, pain characteristics, psychosocial characteristics, and physical characteristics should be included in addressing children and adolescents with musculoskeletal pain.Trial registrationThe ChiBPS study where the participants in this study are from, was pre-registered before recruitment (ClinicalTrials.gov Identifier: NCT03678922) date: 09.20.18.
RETRACTED: Development of a Systematic Course On Orthodontic Temporary Anchorage Devices (TADs) for Orthodontic Residency Program
Authors: Tang Ziwei , Gao Yanzi , Chen Yiyin , Pu Lingling , Liu Lu , Li Xiaolong , Jian Fan , Wang Yan , Lai Wenli , Long Hu
Published: September 2021

The authors have requested that this preprint be removed from Research Square.
Effect of Lanthanum Substrates on the Structural, Optical and Electrical Properties of Copper Selenide Thin Films Designed for 5G Technologies
Authors: Qasrawi Atef , Ghannam Arwa N. Abu
Published: September 2021

In this work, copper selenide thin films coated onto glass and transparent lanthanum substrates are studied. The (glass, La)/CuSe thin films which are prepared by the thermal evaporation technique under a vacuum pressure of 10− 5 mbar are structurally, morphologically, optically, dielectrically and electrically characterized. Lanthanum substrates improved the crystallinity by increasing the crystallite size and decreasing both of the microstrains and defect density of copper selenide. La substrates redshifts the energy band gap and doubled the dielectric constant values. In addition, employing Drude-Lorentz approaches for optical conduction to fit the dielectric constant provided information about the effects of La substrates on the drift mobility, plasmon frequency, free carrier density and scattering times at femtosecond level. The drift mobility increased and the plasmon frequency range is modified when La substrates are used. Verifying impedance spectroscopy test in the microwave frequency domain have shown that the La(gate)/CuSe/Ag (source) transistors can be employed as band pass filter suitable for 5G technologies. The microwave cutoff frequency reached ~ 5.0 GHz at a notch frequency of 2.80 GHz of the La/CuSe/Ag highpass filters.
Structurally Integrated Properties of Random, Uni-Directional, and Bi-Directional Freeze-Dried Cellulose/Chitosan Aerogels
Authors: Chaudary Aneeba , Patoary Mohammed Kayes , Zhang Meiling , Chudhary Tayba , Farooq Amjad , Liu Lifang
Published: September 2021

Aerogels as a thermally insulating material have attracted extensive consideration in recent years due to prevailing energy consumption in building, industrial sector, and aerospace applications. Cellulose contains all the favorable properties to be used as a thermally resistant substance but due to structural instability, it needs to be impregnated with other resilient substances. We report herein the preparation of cellulose nanofiber (CNF)/chitosan (CS) isotropic and anisotropic composite aerogels (CCSA) by employing three different: random, uni-directional, and bi-directional freezing techniques, ensuing freeze-drying process to investigate the structural modification effect on the thermal and mechanical properties. Aerogels behaved distinctively along different axis due to holding entirely eccentric porous micro-orientation along lateral (perpendicular to ice growth) and axial (parallel to ice growth) directions. Randomly frozen aerogels (r-CCSA) contained uneven porous networks because of random ice crystal formation within the microstructure and resulted in isotropic characteristics with thermal conductivity (λ) of 0.038Wm-1K-1 in both axial and radial direction. whereas unidirectional frozen aerogels (u-CCSA) exhibited anisotropic microstructure and performance with lamellas in axial and honeycombed in radial direction resulting in λ value of 0.040 Wm-1K-1 and 0.034 Wm-1K-1 respectively. Similarly, the controlled temperature gradient during the preparation of bidirectional aerogels (b-CCSA) presented an anisotropic sheet-like microstructure and resulted in ultra-low thermal conductivity along the axial and radial geometry with λ of 0.33 Wm-1K-1 and 0.027 Wm-1K-1 respectively because of the Knudsen effect. CCSA reported in this work resulted in ultra-low density (5 to 16 mgcm-3), high porosity (~99.6%), and robustness mechanically with an endurance of 60% strain. Such a composite bio-mass aerogel preparation method will offer a clear insight into the adoption of the right methodology according to target practical applications with consideration of environmental safety.
ProteinUnet2 for Fast Protein Secondary Structure Prediction: A Step Towards Proper Evaluation
Authors: Stapor Katarzyna , Kotowski Krzysztof , Smolarczyk Tomasz , Roterman Irena
Published: September 2021

Background: The importance of protein secondary structure (SS) prediction is widely known, its solution enables learning about the role of a protein in organisms. As the experimental methods are expensive and sometimes impossible, many SS predictors, mainly based on different machine learning methods have been proposed for many years. SS prediction as the imbalanced classification problem should not be judged by the commonly used Q3/Q8 metrics. Moreover, as the benchmark datasets are not random samples, the classical statistical null hypothesis testing based on the Neyman-Pearson approach is not appropriate. Also, the state-of-the-art predictors have usually relatively long prediction times.Results: We present a new deep network ProteinUnet2 for SS prediction which is based on U-Net convolutional architecture. We also propose a new statistical methodology for prediction performance assessment based on the significance from Fisher-Pitman permutation tests accompanied by practical significance measured by Cohen’s effect size. Through an extensive evaluation study, we report the performance of ProteinUnet2 in comparison with two state-of-the-art methods SAINT and SPOT-1D on benchmark datasets TEST2016, TEST2018, and CASP12. Conclusions: Our results suggest that ProteinUnet2 has much shorter prediction times while maintaining (or outperforming) the mentioned predictors. We strongly believe that our proposed statistical methodology will be adopted and used (and even expanded) by the research community.
Symptoms of Depression Change With Olfactory Functions
Authors: Sabiniewicz Agnieszka , Hoffman Leonie , Haehner Antje , Hummel Thomas
Published: September 2021

Olfactory loss is associated with symptoms of depression. The present study, conducted on a large cohort of mostly dysosmic patients, aimed to investigate whether improvement in olfactory performance would correspond with a decrease in depression severity and, if so, to what extent. In 171 participants, we assessed olfactory function and severity of depression before and after an average interval of 11 months, with many patients improving in function. Separate analyses were conducted for a) the whole group of patients and b) the group of dysosmic patients in both classic and Bayesian ways. Student t-test demonstrates that the whole sample improved consistently, especially within the group of dysosmic patients in terms of odor identification, and the dysosmic group also improved in terms of odor threshold and olfactory functions in general. Pearson correlation showed that the increase in olfactory functions corresponded with the decrease in depression severity, particularly in dysosmic patients. To conclude, the present study results indicate that symptoms of depression change with olfactory functions in general and odor identification in particular.
Evidence for an FMR1 mRNA Gain-Of-Function Toxicity Mechanism in the Pathogenesis of Fragile-X Associated Premature Ovarian Insufficiency
Authors: Rosario Roseanne , Stewart Hazel , Choudhury Nila Roy , Michlewski Gracjan , Charlet-Berguerand Nicolas , Anderson Richard (A)
Published: September 2021

Fragile X-associated premature ovarian insufficiency (FXPOI) is caused by expansion of a CGG repeat sequence located in the 5’ untranslated region of the FMR1 gene. Women with FXPOI have a depleted ovarian reserve, resulting in amenorrhea, hypoestrogenism, and loss of fertility before the age of 40. FXPOI is caused by CGG sequence expansions to lengths between 55 and 200 repeats, known as a FMRI premutation, however the mechanism by which the premutation drives disease pathogenesis remains unclear. Two main hypotheses exist, which describe an mRNA toxic gain-of-function mechanism or that repeat-associated non-AUG (RAN) translation results in the production of an abnormal protein, called FMRpolyG. We have developed an in vitro granulosa cell model of the FMR1 premutation by ectopically expressing CGG-repeat RNA and FMRpolyG protein. We show that expanded CGG-repeat RNA accumulated in intranuclear RNA structures, and these aggregates were able to cause significant granulosa cell death independent of FMRpolyG expression. Furthermore, using an innovative RNA pulldown, mass spectrometry-based approach we have identified proteins that bind CGG-repeat RNA in granulosa cells in vitro, and thus may be deregulated as consequence of this interaction. Collectively, these data provide evidence for the contribution of an mRNA gain-of-function mechanism to FXPOI disease biology.
Detection of SARS-CoV-2 infection by microRNA profiling of the upper respiratory tract
Authors: Farr Ryan , Rootes Christina , Stenos John , Foo Chwan Hong , Cowled Christopher , Stewart Cameron
Published: September 2021

Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases with 99.9% accuracy. Here we sought to develop a signature suited for clinical application by analyzing specimens collected using minimally invasive procedures. Eight miRNAs displayed altered expression in anterior nasal tissues from COVID-19 patients, with miR-142-3p, a negative regulator of interleukin-6 (IL-6) production, the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-30c-2-3p, miR-628-3p and miR-93-5p) independently classifies COVID-19 cases with 100 % accuracy. This study further defines the host miRNA response to SARS-CoV-2 infection and identifies candidate biomarkers for improved COVID-19 detection.
Dual Hyaluronic Acid and Folic Acid Targeting pH-Sensitive Multifunctional 2DG@DCA@MgO-Nano-Core-Shell-Radiosensitizer for Breast Cancer Therapy
Authors: Askar Mostafa A. , Thabet Noura Magdy , El-sayyad Gharieb S. , El-Batal Ahmed I. , kodous Mohamed abd El , Kawamura Go , Matsuda Atsunori , Shawi Omama E. El , Helal Hamed , Abdel-Rafei Mohamed Khairy
Published: September 2021

Background: Globally, breast cancer (BC) poses a serious public health risk. The disease exhibits a complex heterogeneous etiology and is associated with glycolysis and oxidative phosphorylation (OXPHOS) metabolic reprograming pathways which fuel proliferation and progression. Due to the late manifestation of symptoms, rigorous treatment regimens are required following diagnosis. Existing treatments are limited by a lack of specificity, systemic toxicity, temporary remission, and radio-resistance in BC. In this study, we developed CD44 and folate receptor-targeting multi-functional dual drug-loaded nanoparticles (DDM). These contained a hyaluronic acid (HA) and folic acid (FA) conjugated to a dichloroacetate (DCA) shell linked to a 2-deoxy glucose (2DG) and magnesium oxide (MgO) core to enhance localized chemo-radiotherapy for effective BC treatment.Methods: The physicochemical properties of nanoparticles, including stability, selectivity, release in response to pH, cellular uptake, and anticancer efficacy were comprehensively examined. Mechanistically, we identified multiple component signal pathways as important regulators of BC metabolism and mediators of inhibitory effects toward DDM.Results: Nanoparticles exhibited sustained DDM release properties in bio-relevant media, which was responsive to acidic pH providing ﬂexibility to the control of drug release from nanoparticles. DDM-loaded and HA-FA-functionalized nanoparticles exhibited increased selectivity and uptake by BC cells. Cells study indicated that functionalized DDM significantly suppressed cancer cell growth and radiotherapy (RT) improvement via cell cycle arrest, apoptosis enhancement, and modulation of glycolysis and OXPHOS pathways.Conclusions: By highlighting DDM mechanisms as an antitumor and radio-sensitizing reagent, our analysis also revealed glycolysis and OXPHOS modulation via PI3K/AKT/mTOR/NF-κB/VEGFlow and P53high signal pathways. In conclusion, we indicated that multi-functionalized DDM depletion-mediated metabolic reprogramming via multiple signal pathways in BC cells is a promising targeted metabolic therapy.
Effect of Deploying Biomedical Equipment Technician on the Functionality of Medical Equipment in the Government Hospitals of Rural Nepal
Authors: Thapa Rita , Yih Alison , Chauhan Ashish , Poudel Salomi , Singh Sagar , Shrestha Suresh , Tamang Suresh , Shrestha Rishav , Rajbhandari Ruma
Published: September 2021

Background: Medical equipment plays a crucial role in the provision of quality healthcare services, despite this more than 50% of equipment in developing countries are non-functioning due to a lack of appropriate human resources to maintain. To address this problem some government hospitals of Nepal have deployed a mid-level technical cadre called 'Biomedical Equipment Technician' (BMET). This study aims to evaluate the effectiveness of deploying a BMET on the functionality of medical equipment in government hospitals of rural Nepal.Methods: We used a mixed-methods approach with a comparative research design. A comprehensive range of 2189 pieces of medical equipment at 22 hospitals with and without BMET were observed to assess their functional status. Medical equipment were stratified into 6 categories based on department and T-tests were conducted. We collected qualitative data from 9 BMETs, 22 medical superintendents, and 22 health staff using semi-structured interviews and focus-group discussions. Thematic content analysis was conducted to explore how the BMET's work was perceived.Findings: The quantity of non-functional devices in hospitals without BMETs was double that of hospitals with BMETs (14% and 7% respectively, p<0.005). Results were similar across all departments including General (16% versus 3%, p=0.056), Lab (15% versus 7%, p<0.005) and Operation Theater (14% versus 5%, p<0.005). Hospitals with BMETs had fewer overall non-functional devices requiring simple or advanced repair compared to hospitals without BMETs [3% versus 7% (p<0.005) simple; 4% versus 6% (p < 0.005) advanced]. In our qualitative analysis, we found that BMETs were highly appreciated by hospital staff. Hospital workers perceived that having a BMET on staff, rather than twice-yearly visits from central-level maintenance technicians, is an effective way to keep medical equipment functional. However, without a favorable working environment, the BMET alone cannot perform optimally. Conclusions: Having a BMET at a rural government hospital has a substantial positive effect on the functional status of medical devices at the hospital. BMETs should be deployed at all rural hospitals to increase the functionality of medical devices, thereby improving the working environment and quality of health services provided.
ALPN-101 (Acazicolcept) a Dual ICOS/CD28 Antagonist, Demonstrates Efficacy in Systemic Sclerosis Preclinical Mouse Models
Authors: Orvain Cindy , Cauvet Anne , Prudent Alexis , Guignabert Christophe , Thuillet Raphaël , Ottaviani Mina , Tu Ly , Duhalde Fanny , Nicco Carole , Batteux Frédéric , Avouac Jérôme , Wang NinXin , Seaberg Michelle A. , Dillon Stacey R. , Allanore Yannick
Published: September 2021

BackgroundUncontrolled immune response with T cell activation has a key role in the pathogenesis of systemic sclerosis (SSc), a disorder that is characterised by generalized fibrosis affecting particularly the lungs and skin. Co-stimulatory molecules are key players during immune activation, and recent evidence supports a role of CD28 and ICOS in the development of fibrosis. We herein investigated the efficacy of ALPN-101 (acazicolcept), a dual ICOS/CD28 antagonist, in two complementary SSc-related mouse models recapitulating skin fibrosis, interstitial lung disease, and pulmonary hypertension. MethodsExpression of circulating soluble ICOS and skin-expressed ICOS was investigated in SSc patients. Thereafter, ALPN-101 was evaluated in the hypochlorous acid (HOCL)-induced dermal fibrosis mouse model and in the Fra-2 transgenic (Tg) mouse model. In each model, mice received 400 µg of ALPN-101 or a molar-matched dose of an Fc control protein twice a week for six weeks. After six weeks, skin and lung were evaluated.Results ICOS was significantly increased in the sera from SSc patients and in SSc skin biopsies as compared to samples from healthy controls. Similar body weight changes were observed between Fc Control and ALPN-101 groups in both HOCL and Fra-2 Tg mice suggesting a good tolerance of ALPN-101 treatment. In mice challenged with HOCL, ALPN-101 induced a significant decrease in dermal thickness, collagen content, myofibroblast number and inflammatory infiltrates characterized by B cells, T cells, neutrophils, and macrophages. In the Fra-2 Tg mouse model, ALPN-101 treatment reduced lung collagen content, fibrillar collagen, histological fibrosis score, and right ventricular systolic pressure (RVSP). A reduction in frequency of CD4+ and T effector memory cells and an increase in the percentage of CD4+ T naïve cells in spleen and lung of ALPN-101-treated Fra-2 Tg mice was observed as compared to Fc control-treated Fra-2 Tg mice. Moreover, ALPN-101 reduced CD69 and PD-1 expression on CD4+ T cells from the spleen and the lung. Target engagement by ALPN-101 was demonstrated by blockade of CD28 and ICOS detection by flow cytometry in treated mice. Conclusions Our results confirm the importance of co-stimulatory molecules in inflammatory-driven fibrosis. Our data highlight a key role of ICOS and CD28 in SSc. Using complementary models, we demonstrated that dual ICOS/CD28 blockade by ALPN-101 decreased dermal and pulmonary fibrosis and alleviated pulmonary hypertension. These results pave the way for subsequent research on ICOS/CD28-targeted therapies.
Widespread global concern over harm from drinking water
Authors: Young Sera , Miller Joshua , Staddon Chad , Salzberg Aaron , Lucks Julius , de Bruin Wändi Bruine
Published: September 2021

Poor drinking water quality is a global crisis that affects billions of individuals. Understanding who is most impacted is necessary to develop programs that ensure sustainable, reliable, and resilient access to safe water. But current water indicators do not capture people’s experienced and anticipated harm from drinking water, which means we have had limited understanding of how individuals conceptualize, navigate, and are affected by their water environment. Here, we analyzed data from nationally representative surveys undertaken in 142 countries in which people reported their recent experiences and future expectations of harm from drinking water. Prevalence of reported harm from drinking water in the prior two years was 14.5% (range: 0.8%–54.3%). More than half of the world’s population (54.4%) anticipated that they would experience serious harm from their drinking water in the next two years. Greater public sector corruption was associated with greater anticipated harm from drinking water, even when adjusting for indicators of water infrastructure and economic development. Disparities in anticipated harm across countries and by gender and household location indicate that targeted policies are required to address risk perceptions, equitably improve access to safe drinking water, and increase trust in institutions that supply and regulate water services. The addition of experiential survey data to global data collection efforts will complement objective water quality data and provide novel insights about which strategies will most effectively advance progress toward safe drinking water for all.
Tumor Remnant After Silicone Implant en Block Capsulectomy: The Magnetic Resonance Role
Authors: Fleury Eduardo Faria Castro
Published: September 2021

Recently, there has been an increase in surgeries to treat silicone implants complications. These procedures are generally related to diseased fibrous capsules, whose most common clinical manifestation is capsular contracture. Other frequently found presentations are intracapsular collection and local inflammatory signs. The causes of these complications are not well established. Some reports associate them with the implant texture, gel bleeding, silicone-induced granuloma, and infectious processes. Although rare, there is an association with malignant neoplasia in the literature, where Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is the most severe complication. Patients often do not perform a Magnetic Resonance (MRI) scan for the explant surgical programming.The accuracy of MRI to assess fibrous capsule tumor remnants depends on the surgical time. The ideal time for the evaluation is up to 72 hours after the surgical time when the repair tissue starts to appear. Up to 2-3 weeks after surgery, MRI can provide information regarding the presence of a residual tumor. After this period, the presence of scar tissue impairs the analysis. This short report discusses the role of MRI in the evaluation of residual fibrous capsules in the postoperative period.
Microbiota in Mesenteric Adipose Tissue From Crohn’s Disease Promote Colitis in Mice
Authors: He Zhen , Wu Jinjie , Gong Junli , Ke Jia , Ding Tao , Zhao Wenjing , Cheng WaiMing , Luo Zhanhao , He Qilang , Zeng Wanyi , Yu Jing , Jiao Na , Liu Yanmin , Zheng Bin , Dai Lei , Zhi Min , Wu Xiaojian , Jobin Christian , Lan Ping
Published: September 2021

Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat is a pathologic characteristic of Crohn’s disease (CD). The reserve of creeping fat in surgery is associated with poor prognosis of CD patients, but the mechanism remains unknown.Methods: Mesenteric microbiome, metabolome and host transcriptome were characterized using a cohort of 48 patients with CD and 16 non-CD controls. Multidimensional data including 16S ribosomal RNA gene sequencing (16S rRNA), host RNA sequencing and metabolome were integrated to reveal network interaction. Mesenteric resident bacteria were isolated from mAT and functionally investigated both in dextran sulfate sodium (DSS) model and Il10 gene deficient (Il10-/-) mouse colitis model to validate their pro-inflammatory roles. Results: Mesenteric microbiota contributed to aberrant metabolites production and transcripts in mATs from patients with CD. Presence of mAT resident microbiota was associated with the development of CD. Achromobacter pulmonis (A. pulmonis) isolated from CD mAT could translocate to mAT and exacerbate both DSS-induced and Il10 gene deficient (Il10-/-) spontaneous colitis in mice. The levels of A. pulmonis both in mAT and mucous layer from CD patients were higher compared to those from non-CD group. Conclusions: This study suggests that the mesenteric microbiota from patients with CD sculpt a detrimental microenvironment and promote intestinal inflammation.
Numerical and Experimental Investigation of Formability in Incremental Sheet Forming of Particle Reinforced Metal Matrix Composite Sheets
Authors: Gatea Shakir , Tawfiq Thana Abdel Salam , Ou Hengan
Published: September 2021

Metal matrix composites (MMCs) have a high strength-to-weight ratio, high stiffness, and good damage resistance under a wide range of operating conditions, making them a viable alternative to traditional materials in a variety of technical applications. Because of their high strength, composite materials are hard to deform to a significant depth at room temperature. As a result, additional treatments are required to enhance the composite's room ductility prior to deformation. In this investigation, as-received 6092Al/SiCp composite sheets (T6-condition) are heat treated to O-condition annealing to enhance its ductility in order to assess the influence of single point incremental forming (SPIF) parameters on the formability and fracture behavior of the Al/SiC particle composite sheets at room temperature. Then the annealed sheets are heat treated to T6-condition to enhance the strength and achieve properties equivalent to as-received sheets properties. The results demonstrate that the Al/SiC particle composite sheets with T6 treatment could not be deformed to the specified depth at room temperature due to low room ductility and that further treatment, such as O-condition annealing, is required to enhance the room ductility. When annealed Al/SiCp composite sheets are heat treated to T6, the sheets exhibit properties comparable to the as-received sheets. Al/SiC particle composite sheets with low SPIF parameters may have greater formability and fracture depth with low strain hardening curve.
TGF-β associated senescence and impaired metabolism in central memory CD4 T cells promotes HIV persistence
Authors: Sekaly Rafick , Ghneim Khader , Sharma Ashish , Ribeiro Susan , Fourati Slim , Ahlers Jeffery , Kulpa Deanna , Xu Xuan , Brehm Jessica , Talla Aarthi , Rodriguez Benigno , Shive Carey , Cristescu Razvan , Loboda Andrey , Balderas Robert , Wang I-ming , Hunt Peter , Lamarre Daniel , Douek Daniel , Hazuda Daria , Lederman Michael , Deeks Steven
Published: September 2021

Current therapeutic interventions to eradicate latent HIV (“reservoir”) and restore immune function in ART-treated HIV infection have yet to show efficacy. To explore mechanisms of HIV persistence, we apply an integrated systems biology approach and identify a distinct group of individuals with poor CD4 T-cell reconstitution (Immunologic non-responders, “INRs”) and high frequencies of cells with inducible HIV. Contrary to the prevailing notion that immune activation drives HIV persistence and immune dysfunction, peripheral blood leukocytes from these subjects have enhanced expression of a network of genes regulated by cellular senescence. In these subjects, increased frequencies of regulatory T cells and expression of the TGF-β signaling cascade are concomitant with the downregulation of cell cycle and metabolism in CD4 central memory T (TCM) cells. These cascades, downstream of TGF-β, lead to the accumulation of PD-1 expressing CD4 TCM and are associated with an increase in frequencies of cells with inducible HIV ex vivo. In vitro validation confirmed that this cellular profile was driven by a β-hydroxybutyrates/bile acid rich metabolic milieu and resulted in TGF-β associated latency establishment. Our findings identify targets for PD-1 or TGF-β specific interventions that can overcome cellular senescence; these therapeutic approaches have shown safety and efficacy in cancer, and may prove to be crucial for HIV eradication.