bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study
Authors: Zhang Lei , Yun Shuang , Wu Tiange , He Yujie , Guo Jinyan , Han Lishuai , Lu Jiameng , Liu Xiaojun , Yang Rui , Zhang Shitao , Li Tianfang , Liu Shengyun
Published: May 2021

Background

Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC.

Results

Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = − 0.75, P < 0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, a minority of limited RPC patients progressed into systemic form. Patients with Ear pattern had the highest survival rate and relatively lower inflammatory status.

Conclusions

RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement. The clinical patterns and presenting forms may evolve during follow-up. Our findings may facilitate early recognition of this rare disease.
Lung histopathological findings in COVID-19 disease – a systematic review
Authors: Pannone Giuseppe , Caponio Vito Carlo Alberto , De Stefano Ilenia Sara , Ramunno Maria Antonietta , Meccariello Mario , Agostinone Alessio , Pedicillo Maria Carmela , Troiano Giuseppe , Zhurakivska Khrystyna , Cassano Tommaso , Bizzoca Maria Eleonora , Papagerakis Silvana , Buonaguro Franco Maria , Advani Shailesh , Muzio Lorenzo Lo
Published: May 2021

Since December 2019, the global burden of the COVID-19 pandemic has increased rapidly and has impacted nearly every country in the world, affecting those who are elderly or with underlying comorbidities or immunocompromised states. Aim of this systematic review is to summarize lung histopathological characteristics of COVID-19, not only for diagnostic purpose but also to evaluate changes that can reflect pathophysiological pathways that can inform clinicians of useful treatment strategies. We identified following histopathological changes among our patients:: hyaline membranes; endothelial cells/ interstitial cells involvement; alveolar cells, type I pneumocytes/ type II pneumocytes involvement; interstitial and/ or alveolar edema; evidence of hemorrhage, of inflammatory cells, evidence of microthrombi; evidence of fibrin deposition and of viral infection in the tissue samples.

The scenario with proliferative cell desquamation is typical of Acute Respiratory Distress Syndrome (ARDS) that can be classified as diffuse alveolar damage (DAD) and not DAD-ARDS. The proposed pathological mechanism concerns the role of both innate and adaptive components of the immune system. COVID-19 lethal cases present themselves as a heterogeneous disease, characterized by the different simultaneous presence of different histological findings, which reflect histological phases with corresponding different pathological pathways (epithelial, vascular and fibrotic changes), in the same patient.
Tools for measuring gender equality and women’s empowerment (GEWE) indicators in humanitarian settings
Authors: Goulart Céline M. , Purewal Amber , Nakhuda Humaira , Ampadu Anita , Giancola Amanda , Kortenaar Jean-Luc , Bassani Diego G.
Published: May 2021

Background

Effective measurement of Gender Equality and Women’s Empowerment (GEWE) is challenging in low and middle-income countries (LMICs), and even more so in humanitarian settings. Conflict, natural disasters, and epidemics may increase gender inequities, but also present an opportunity to address them. This scoping review describes and identifies gaps in the measurement tools, methods, and indicators used to measure GEWE in humanitarian settings, and presents a dashboard that can be used by researchers, organizations and governments to identify GEWE measurement tools.

Methods

Scientific articles published between January 2004 and November 2019 were identified using Embase, Medline, PsycInfo, CINAHL, Scopus, and PAIS index. Relevant non peer-reviewed literature was downloaded from the websites of humanitarian organizations. Publications on women and/or girls impacted by a humanitarian crisis in a LMIC, within 5 years of data collection, were included. Publications were double-screened in the title/abstract and full-text stages. We used a machine learning software during the title/abstract screening to increase the efficiency of the process. Measurement tools, sampling and data collection methods, gap areas (geographical, topical and contextual), and indicators were catalogued for easy access in an interactive Tableau dashboard.

Results

Our search yielded 27,197 publications and 2396 non peer-reviewed literature reports. One hundred and seventy publications were included in the final review. Extracted indicators were categorized into seven domains: economic, health, human development, leadership, psychological, security and justice, and sociocultural. The vast majority of studies were observational, and over 70% utilized a cross-sectional study design. Thirty-eight toolkits and questionnaires were identified in this review, of which 19 (50%) were designed specifically for humanitarian settings. Sociocultural was the largest domain in number of studies and indicators in this review, with gender-based violence indicators reported in 66% of studies. Indicators of economic, human development and leadership were uncommon in the peer-reviewed literature.

Discussion

While there has been some effort to measure GEWE in conflict-affected and other humanitarian settings, measurement has largely focused on violence and security issues. A more comprehensive framework for measuring GEWE in these settings is needed; objective measurement of women’s empowerment and gender equality should be prioritized by organizations providing humanitarian aid.
Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer
Authors: Chen Gong , Peng Junjie , Xiao Qian , Wu Hao-Xiang , Wu Xiaojun , Wang Fulong , Li Liren , Ding Peirong , Zhao Qi , Li Yaqi , Wang Da , Shao Yang , Bao Hua , Pan Zhizhong , Ding Ke-Feng , Cai Sanjun , Wang Feng , Xu Rui-Hua
Published: May 2021

Background

Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.

Methods

From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.

Results

Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.

Conclusions

Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.
Randomised controlled trials in pre-hospital trauma: a systematic mapping review
Authors: Björklund Matilda K. , Cruickshank Moira , Lendrum Robbie A. , Gillies Katie
Published: May 2021

Background

Trauma is a leading cause of morbidity and mortality worldwide with about 5.8 million deaths globally and the leading cause of death in those aged 45 and younger. The pre-hospital phase of traumatic injury is particularly important as care received during this phase has effects on survival. The need for high quality clinical trials in this area has been recognised for several years as a key priority to improve the evidence base and, ultimately, clinical care in prehospital trauma. We aimed to systematically map the existing evidence base for pre-hospital trauma trials, to identify knowledge gaps and inform decisions about the future research agenda.

Methods

A systematic mapping review was conducted first employing a search of key databases (MEDLINE, CINAHL, EMBASE, and Cochrane Library from inception to March 23rd 2020) to identify randomised controlled trials within the pre-hospital trauma and injury setting. The evidence ‘map’ identified and described the characteristics of included studies and compared these studies against existing priorities for research. Narrative description of studies informed by analysis of relevant data using descriptive statistics was completed.

Results

Twenty-three eligible studies, including 10,405 participants across 14 countries, were identified and included in the systematic map. No clear temporal or geographical trends in publications were identified. Studies were categorised into six broad categories based on intervention type with evaluations of fluid therapy and analgesia making up 60% of the included trials. Overall, studies were heterogenous with regard to individual interventions within categories and outcomes reported. There was poor reporting across several studies. No studies reported patient involvement in the design or conduct of the trials.

Conclusion

This mapping review has highlighted that evidence from trials in prehospital trauma is sparse and where trials have been completed, the reporting is generally poor and study designs sub-optimal. There is a continued need, and significant scope, for improvement in a setting where high quality evidence has great potential to make a demonstrable impact on care and outcomes.
Nutrition-focused group intervention with a strength-based counseling approach for people with clinical depression: a study protocol for the Food for Mind randomized controlled trial
Authors: Roponen Johanna , Ruusunen Anu , Absetz Pilvikki , Partonen Timo , Kuvaja-Köllner Virpi , Hujo Mika , Nuutinen Outi
Published: May 2021

Background

Depression is a highly prevalent mental disorder with major public health effects globally. It impairs the quality of life and reduces the ability to work and function, leading to increasing costs of sick leaves and disability pensions. Current treatment strategies focus on biological and psychological pathways while understating the role of lifestyle factors. Epidemiological studies have shown convincing evidence of an inverse relationship between diet quality and depression. However, only limited data are available on the therapeutic effects of diet quality improvement on depression. Using a randomized controlled trial design, our primary aim is to investigate the effectiveness and cost-effectiveness of a behavioral nutrition group intervention compared to a social support intervention in the treatment of depression.

Methods

Participants (N=144, aged 20–65 years) with a diagnosis of moderate or severe depression recruited in collaboration with outpatient care units will be randomized into two arms: Food for Mind (FM) nutrition intervention (n=72) or Bring Good Mood (BGM) social support control group (n=72). Both arms will be provided with 6 group sessions over an 8-week period. FM involves improving diet quality by applying strength-based behavioral nutrition counseling and activities facilitated by a registered dietitian. The control arm comprises a befriending protocol. During the interventions, all participants will continue their treatment for depression as usual. Longitudinal data are collected at baseline, at 8 weeks, and at 6- and 12-month follow-ups. Depressive symptoms, diet quality, eating behavior, ability to work and function, and quality of life are assessed by self-reported questionnaires. A treatment expectancy questionnaire will be administered at baseline and an acceptability questionnaire at 8 weeks. The Center for Epidemiologic Studies Depression Scale is used as the primary endpoint at 1 year. The results will be analyzed with linear mixed-effects models. Economic evaluation includes both cost-effectiveness and cost-utility analysis. Two incremental cost-effectiveness ratios will be calculated to evaluate the incremental cost per QALY and the incremental cost per improvement in CES-D.

Discussion

If the intervention proves to be cost-effective and acceptable, it be can be implemented in healthcare to support the treatment of depression.

Trial registration

ClinicalTrials.gov NCT03904771. Retrospectively registered on 5 April 2019
Parent engagement in co-design of clinical trials: the PARENT trial
Authors: Vanderloo Leigh M. , Vanderhout Shelley M. , Tavares Erika , Maguire Jonathon , Straus Sharon , Birken Catherine S.
Published: May 2021

Evidence generated from partnering with parents to design and conduct research together may be used to refine, adjust, and modify future research approaches. This study aimed to describe the initial approaches to parent engagement in the design of the PARENT trial as well as understand parent perspectives on the acceptability and relevance of the PARENT trial and potential barriers and facilitators to participation.

Parents participating in the TARGet Kids! cohort were invited to participate in a focus group, called the PARENT panel, to co-design the PARENT trial. This focus group was conducted to capture diverse individual and collective parents’ experiences. Overall methodological approaches for the PARENT panel were informed by the CIHR Strategy for Patient Oriented Research (SPOR) guiding principles (mutual respect, co-building, inclusiveness, and support) for patient engagement in research, and facilitated through the Knowledge Translation Program in the Li Ka Shing Knowledge Institute at Unity Health Toronto. Using a Nominal Group Technique, the PARENT panel provided feedback on the feasibility, relevance, and acceptability of the proposed intervention. Findings from this work will be used to further refine, adjust, and modify the next iteration of the PARENT trial, which will also serve as an opportunity to discuss the efforts made by researchers to incorporate parent suggestions and what additional steps are required for improved patient engagement.
Effectiveness of Credelio® Plus, a novel chewable tablet containing milbemycin oxime and lotilaner for the treatment of larval and immature adult stages of Toxocara canis in experimentally infected dogs
Authors: Young Lisa M. , Wiseman Scott , Crawley Elizabeth , Bowman Dwight D. , Reinemeyer Craig R. , Snyder Daniel E.
Published: May 2021

Background

The ascarid, Toxocara canis, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. An effective treatment that kills any pre-patent stages of immature T. canis could additionally reduce or eliminate the development of patent infections that can result in clinical disease in infected dogs and would further reduce environmental contamination of eggs. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to assess the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs that were experimentally infected with immature (L4 or immature adult [L5]) stages of T. canis.

Methods

The commercial tablet formulation of Credelio Plus® was administered in a time frame relative to inoculation with infective eggs. This allowed for effectiveness to be assessed against each specific immature stage of T. canis. In each study, dogs were randomized and allocated to one of four treatment groups. Each treatment group contained ten dogs that had been experimentally inoculated on Day 0 with infective T. canis eggs and then were dosed once on Day 14 or Day 24 using either placebo tablets or Credelio Plus tablets (IP) to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 or 6 days after their respective treatment. At necropsy, all nematodes recovered from the gastrointestinal tract were counted by species and stage.

Results

In both dose confirmation studies using geometric mean worm counts, effectiveness of Credelio Plus was ≥ 98.6% and ≥ 96.8% against L4 larval stage T. canis and immature adult [L5] T. canis in both studies, respectively.

Conclusions

These studies demonstrated that the Credelio Plus combination tablet administered orally to dogs was highly efficacious against experimental infections with L4 and immature adult [L5] stages of T. canis.

Graphical Abstract
Effects of Zataria multiflora essential oil on the germinative cells of Echinococcus granulosus
Authors: Kowsari Nasim , Moazeni Mohammad , Mohammadi Ali
Published: May 2021

Background

Novel and more efficient compounds are urgently required for medical treatment of cystic echinococcosis (CE). Germinative cell culture of Echinococcus granulosus could be used for anti-echinococcosis agent tests and other biological studies on CE. This study was performed to establish an in vitro cell culture model for E. granulosus germinative cells and to evaluate the lethal effect of Zataria multiflora essential oil (ZMEO) on the cultured cells.

Methods

The inner surface of germinal layers of CE cysts was scraped, and the obtained materials were trypsinized to obtain a suspension of single germinative cells. Medium 199 was used as the basic culture medium and was supplemented with fetal bovine serum, 2-mercaptoethanol, l-cysteine, l-glutamine, glucose, sodium pyruvate, hydatid fluid, amphotericin B and antibiotics. The cells were cultured at a concentration of 104 cells/ml of culture medium and incubated at 37 °C. The culture medium was replaced every 7 days. Chemical composition of ZMEO was identified by GC-MS analysis. ZMEO was tested at concentrations of 0.5–8 mg/ml. Viability of the cells was assessed by trypan blue exclusion assay.

Results

A significant increase in the cell number was evident at 20, 30 and 45 days after cultivation. At 45 days of cultivation, the number of cells was approximately five-fold higher than on the first day. In GC-MC analysis, carvacrol, p-cymene, g-terpinene and thymol were found to be the main compounds of ZMEO. The lethal effect of ZMEO on the germinative cells at concentrations of 6, 7 and 8 mg/ml was 100% after 60, 25 and 7 min of exposure, respectively.

Conclusions

At 45 days of cultivation, the cell concentration was suitable for the desired in vitro experiments. A high lethal effect of ZMEO on the germinative cells of E. granulosus may be considered an opportunity for the introduction of a novel, more effective and safer therapeutic agent for treatment of CE using an herbal product.

Graphical Abstract
MMP-2 is a novel histone H3 N-terminal protease necessary for myogenic gene activation
Authors: Rice Judd C. , Weekley Benjamin H. , Kanholm Tomas , Chen Zhihui , Lee Sunyoung , Fernandez Daniel J. , Abrahamson Rachel , Castaldi Alessandra , Borok Zea , Dynlacht Brian D. , An Woojin
Published: May 2021

Background

Selective proteolysis of the histone H3 N-terminal tail (H3NT) is frequently observed during eukaryotic development, generating a cleaved histone H3 (H3cl) product within a small, but significant, portion of the genome. Although increasing evidence supports a regulatory role for H3NT proteolysis in gene activation, the nuclear H3NT proteases and the biological significance of H3NT proteolysis remain largely unknown.

Results

In this study, established cell models of skeletal myogenesis were leveraged to investigate H3NT proteolysis. These cells displayed a rapid and progressive accumulation of a single H3cl product within chromatin during myoblast differentiation. Using conventional approaches, we discovered that the canonical extracellular matrix (ECM) protease, matrix metalloproteinase 2 (MMP-2), is the principal H3NT protease of myoblast differentiation that cleaves H3 between K18-Q19. Gelatin zymography demonstrated progressive increases in nuclear MMP-2 activity, concomitant with H3cl accumulation, during myoblast differentiation. RNAi-mediated depletion of MMP-2 impaired H3NT proteolysis and resulted in defective myogenic gene activation and myoblast differentiation. Supplementation of MMP-2 ECM activity in MMP-2-depleted cells was insufficient to rescue defective H3NT proteolysis and myogenic gene activation.

Conclusions

This study revealed that MMP-2 is a novel H3NT protease and the principal H3NT protease of myoblast differentiation. The results indicate that myogenic signaling induces MMP-2-dependent H3NT proteolysis at early stages of myoblast differentiation. Importantly, the results support the necessity of nuclear MMP-2 H3NT protease activity, independent of MMP-2 activity in the ECM, for myogenic gene activation and proficient myoblast differentiation.
Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes
Authors: Cao Jie , Wang Hong , Su Jian-bin , Wang Xue-qin , Zhang Dong-mei , Wang Xiao-hua , Liu Wang-shu , Ge Xiao-qin
Published: May 2021

Objective

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D.

Methods

This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected.

Results

It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β =  − 0.125, t =  − 5.397, p < 0.001, adjusted R2 = 0.459).

Conclusions

Serum ADA levels are independently associated with islet beta cell function in patients with T2D.
Are caveolin-1 minor alleles more likely to be risk alleles in insulin resistance mechanisms in metabolic diseases?
Authors: Abaj Faezeh , Saeedy Said Abdul Ghafour , Mirzaei Khadijeh
Published: May 2021

Objectives

Obesity and insulin resistance (IR) are interrelated in a range of ways. The IR-obesity relationship is not a cause-and-effect association. Molecular biology research has made tremendous strides in discovering contributors to find this association. Genes that control adipocyte function such as caveolin-1 (CAV1);probably interact in the pathogenesis of human IR in this context. The involvement ofCAV1in glucose/lipid homeostasis is revealed and could modify the signaling of the insulin receptor. We examined the association betweenCAV1and insulin signaling in modifying dyslipidemia and fat composition in overweight and obese women with a prevalent variant in theCAV1gene.

Results

Minor allele carriers were slightly older and had higher BMI (p = 0.02), FMI (p = 0.006), and VLF (p = 0.01) values; and tended to have lower total cholesterol TC (p = 0.04), low-density lipoprotein cholesterol (LDL-C) (p = 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). HOMA-IR levels predicted fat mass index (FMI) 0.47 (0.08, 0.87), visceral fat level (VFL) 0.65 (0.23, 1.07), TC 6.82 (1.76, 11.88) and HDL-C − 1.663 (− 3.11, − 0.214) only between minor allele carriers in adjusted models. (β, CI). Our results cast a new light on the IR mechanism and future studies will elucidate the clinical relevance ofCAV1-IR in patients with dyslipidemia and high fat composition.
The effects of clonidine and yohimbine in the tail flick and hot plate tests in the naked mole rat (Heterocephalus glaber)
Authors: Mwobobia R. M. , Kanui T. I. , Abelson K. S. P.
Published: May 2021

Objective

The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α2) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests.

Results

A significant difference in tail flick latency was noted between saline control and 30 µg/kg clonidine, which was reduced after administration of 30 µg/kg yohimbine. A significant difference in hot plate latency was also noted between saline control and 30 µg/kg clodinine during the periods 30, 45, 60, 75 and 90 min after administration, and between saline control and 10 µg/kg clonidine during 30 min after administration. The hot plate latency by 30 µg/kg clonidine was also reduced by 30 µg/kg yohimbine during 30 min after administration. Since the tail-flick and hot plate tests mediate the effects at spinal and supraspinal levels respectively, the present study indicates the presence and involvement of noradrenergic receptors in thermal antinociception at spinal and supraspinal levels of the NMR, similar to what has been found in other mammals.
Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia’s experience over 26 years
Authors: Noh Lokman Mohd , Latiff Amir Hamzah Abdul , Ismail Intan Hakimah , Noah Rahim Md , Wahab Asrul Abdul , Hamid Intan Juliana Abd. , Ripen Adiratna Mat , Abdullah Nasuruddin B. , Razali Kamarul Azhar , Zainudin Norzila , Bakon Florence , Kok Long Juan , Ali Adli , Aziz Bilkis Banu SAbd , Latif Hasniah Abdul , Mohamad Siti Mardhiana , Zainudeen Zarina Thasneem , Hashim Ilie Fadzilah , Sendut Iean Hamzah , Nadarajaw Thiyagar , Jamil Faizah Mohamed , Ng David C. E. , Abidin Mohd Azri Zainal
Published: May 2021

Background

A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia.

Methods

Data from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed.

Results

Twenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia.

Conclusion

This study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature
Authors: Zhuang Eric , Shane Lisa , Ramezan Nima , Ismail Ameera F. , Vora Nilesh L.
Published: May 2021

Background

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly “peppering” the pons in a perivascular pattern.

Case presentation

Here, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

Conclusions

This case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.
Dynamic thromboembolic left ventricular outflow tract obstruction after aggressive procoagulant treatment in hemorrhagic shock: a case report
Authors: Skrypnikov Vladimir , Rosenthal Christoph , Weber-Carstens Steffen , Menk Mario , Russ Martin
Published: May 2021

Background

In cases of hypertrophic obstructive cardiomyopathy (HOCM), the systolic anterior motion of the mitral valve apparatus results in an obstruction of the left ventricular outflow tract (LVOT), which is known as the SAM [systolic anterior motion] phenomenon. Hypothetically, a pathological obstruction of the LVOT of a different etiology would result in a comparable hemodynamic instability, which would be refractory to inotrope therapy, and may be detectable through echocardiography.

Case presentation

We observed a severely impaired left ventricular function due to a combination of a thrombotic LVOT obstruction and distinctive mitral regurgitation in a 56-year-old Caucasian, female patient after massive transfusion with aggressive procoagulant therapy. Initially, the patient had to be resuscitated due to cardiac arrest after a long-distance flight. The resuscitation attempts in combination with lysis therapy due to suspected pulmonary artery embolism were initially successful but resulted in traumatic liver injury, hemorrhagic shock and subsequent acute respiratory distress syndrome (ARDS). Oxygenation was stabilized with veno-venous extracorporeal membrane oxygenation (ECMO), but the hemodynamic situation deteriorated further. Transesophageal echocardiography (TEE) showed a massive, dynamic LVOT obstruction. Two thrombi were attached to the anterior leaflet of the mitral valve, resulting in a predominantly systolic obstruction. Unfortunately, the patient died of multiple-organ failure despite another round of lysis therapy and escalation of the ECMO circuit to a veno-venoarterial cannulation for hemodynamic support.

Conclusion

Massive transfusion with aggressive procoagulant therapy resulted in mitral valve leaflet thrombosis with dynamic, predominantly systolic LVOT obstruction, comparable to the SAM phenomenon. The pathology was only detectable with a TEE investigation.
Frequency-dependent auto-pooling function for weakly supervised sound event detection
Authors: Liu Sichen , Yang Feiran , Cao Yin , Yang Jun
Published: May 2021

Sound event detection (SED), which is typically treated as a supervised problem, aims at detecting types of sound events and corresponding temporal information. It requires to estimate onset and offset annotations for sound events at each frame. Many available sound event datasets only contain audio tags without precise temporal information. This type of dataset is therefore classified as weakly labeled dataset. In this paper, we propose a novel source separation-based method trained on weakly labeled data to solve SED problems. We build a dilated depthwise separable convolution block (DDC-block) to estimate time-frequency (T-F) masks of each sound event from a T-F representation of an audio clip. DDC-block is experimentally proven to be more effective and computationally lighter than “VGG-like” block. To fully utilize frequency characteristics of sound events, we then propose a frequency-dependent auto-pooling (FAP) function to obtain the clip-level present probability of each sound event class. A combination of two schemes, named DDC-FAP method, is evaluated on DCASE 2018 Task 2, DCASE 2020 Task4, and DCASE 2017 Task 4 datasets. The results show that DDC-FAP has a better performance than the state-of-the-art source separation-based method in SED task.
Neural network-based non-intrusive speech quality assessment using attention pooling function
Authors: Liu Miao , Wang Jing , Yi Weiming , Liu Fang
Published: May 2021

Recently, the non-intrusive speech quality assessment method has attracted a lot of attention since it does not require the original reference signals. At the same time, neural networks began to be applied to speech quality assessment and achieved good performance. To improve the performance of non-intrusive speech quality assessment, this paper proposes a neural network-based assessment method using attention pooling function. The proposed systems are based on the convolutional neural networks (CNNs), bidirectional long short-term memory (BLSTM), and CNN-LSTM structure. Comparing four types of pooling functions both theoretically and experimentally, we find the attention pooling function performs the best among the four. Experiments are conducted in a dataset containing various degraded speech signals with corresponding subjective quality scores. The results show that the proposed CNN-LSTM model using attention pooling function achieves state-of-the-art correlation coefficient (R) and root-mean-square error (RMSE) of 0.967 and 0.269, outperforming the performance of standardization ITU-T P.563 and autoencoder-support vector regression method.
Quaternion fractional-order color orthogonal moment-based image representation and recognition
Authors: He Bing , Liu Jun , Yang Tengfei , Xiao Bin , Peng Yanguo
Published: May 2021

Inspired by quaternion algebra and the idea of fractional-order transformation, we propose a new set of quaternion fractional-order generalized Laguerre orthogonal moments (QFr-GLMs) based on fractional-order generalized Laguerre polynomials. Firstly, the proposed QFr-GLMs are directly constructed in Cartesian coordinate space, avoiding the need for conversion between Cartesian and polar coordinates; therefore, they are better image descriptors than circularly orthogonal moments constructed in polar coordinates. Moreover, unlike the latest Zernike moments based on quaternion and fractional-order transformations, which extract only the global features from color images, our proposed QFr-GLMs can extract both the global and local color features. This paper also derives a new set of invariant color-image descriptors by QFr-GLMs, enabling geometric-invariant pattern recognition in color images. Finally, the performances of our proposed QFr-GLMs and moment invariants were evaluated in simulation experiments of correlated color images. Both theoretical analysis and experimental results demonstrate the value of the proposed QFr-GLMs and their geometric invariants in the representation and recognition of color images.
Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration
Authors: Galán-Ganga M. , Rodríguez-Cueto C. , Merchán-Rubira J. , Hernández F. , Ávila J. , Posada-Ayala M. , Lanciego J. L. , Luengo E. , Lopez M. G. , Rábano A. , Fernández-Ruiz J. , Lastres-Becker I.
Published: May 2021

Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAUP301L overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer’s disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathies.
Foreshock–mainshock–aftershock sequence analysis of the 14 January 2021 (Mw 6.2) Mamuju–Majene (West Sulawesi, Indonesia) earthquake
Authors: Supendi Pepen , Ramdhan Mohamad , Priyobudi  , Sianipar Dimas , Wibowo Adhi , Gunawan Mohamad Taufik , Rohadi Supriyanto , Riama Nelly Florida , Daryono  , Prayitno Bambang Setiyo , Murjaya Jaya , Karnawati Dwikorita , Meilano Irwan , Rawlinson Nicholas , Widiyantoro Sri , Nugraha Andri Dian , Marliyani Gayatri Indah , Palgunadi Kadek Hendrawan , Elsera Emelda Meva
Published: May 2021

We present here an analysis of the destructive Mw 6.2 earthquake sequence that took place on 14 January 2021 in Mamuju–Majene, West Sulawesi, Indonesia. Our relocated foreshocks, mainshock, and aftershocks and their focal mechanisms show that they occurred on two different fault planes, in which the foreshock perturbed the stress state of a nearby fault segment, causing the fault plane to subsequently rupture. The mainshock had relatively few aftershocks, an observation that is likely related to the kinematics of the fault rupture, which is relatively small in size and of short duration, thus indicating a high stress-drop earthquake rupture. The Coulomb stress change shows that areas to the northwest and southeast of the mainshock have increased stress, consistent with the observation that most aftershocks are in the northwest.
The comparison of roof visibility of the mandibular canal between cone-beam computed tomography scans and panoramic radiograph images as dependent on the cortical bone thickness of the mandible
Authors: Ketabi Ali-Reza , Zelka Angeliki , Lauer Hans-Christoph , Hassfeld Stefan
Published: May 2021

Background

Accurate detection of the mandibular canal is a difficult process despite cutting-edge radiographic methods. The present study analyses whether mandibular canal roof visibility is comparable to panoramic radiography (PR) and cone-beam computed tomography (CBCT) and, further, examines whether the visibility in PR and CBCT is dependent on cortical bone thickness in the mandible.

Methods

This study was conducted on a group of 343 selected patients. It incorporated anonymised data on 343 patients in which a CBCT and PR were available. The first stage examines whether the mandibular canal roof visibility is comparable to PR and CBCT. In the second stage, measurements of cortical bone thickness showed buccal and lingual in the P2, M1, M2 and M3 teeth areas, both to the left and right of the mandible in CBCT images.

Statistical analysis was supported by statistical software (IBM SPSS 25; Armonk, NY, USA).

Results

The mean age of the patients was 58.8 years with an almost equal gender distribution. When performing a McNemar test on the P2, M1, M2 and M3 on both the left and right jaws, the difference between the two image modalities, with regard to the visibility of the canal roof, was found to be significant (McNemar test, p < 0.001).

Statistically (U test, p≥0.05), it follows that the thickness of the cortical bone of the mandible exerts no influence on the visibility of the roof of canalis mandibulae in PR and CBCT images.

Conclusion

We conclude that the visibility of the mandibular canal in PR and CBCT rays is not identical, and that the thickness of the cortical bone in the mandible does not represent a factor affecting the visibility of the roof of the mandibular canal.
Risk factors for cutaneous leishmaniasis in a high-altitude forest region of Peru
Authors: Lana Justin T. , Mallipudi Andrés , Ortiz Ernesto J. , Arevalo Jairo H. , Llanos-Cuentas Alejandro , Pan William K.
Published: May 2021

Background

American cutaneous leishmaniasis (CL) is a neglected tropical disease typically associated with men working in remote, sylvatic environments. We sought to identify CL risk factors in a highly deforested region where anecdotal reports suggested an atypical proportion of women and children were infected with CL raising concern among authorities that transmission was shifting towards domestic spaces and population centers.

Methods

We describe the characteristics of CL patients from four participating clinics after digitizing up to 10 years of patient data from each clinic’s CL registries. We assessed risk factors of CL associated with intradomestic, peridomestic, or non-domestic transmission through a matched case-control study with 63 patients who had visited these same clinics for CL (cases) or other medical reasons (controls) between January 2014 and August 2016. The study consisted of an in-home interview of participants by a trained field worker using a standard questionnaire. Risk factors were identified using bivariable and multivariable conditional logistic regression.

Results

Between 2007 and 2016, a total of 529 confirmed CL positives were recorded in the available CL registries. Children and working aged women made up 58.6% of the cases. Our final model suggests that the odds of sleeping in or very near an agricultural field were five times greater in cases than controls (p = 0.025). Survey data indicate that women, children, and men have similar propensities to both visit and sleep in or near agricultural fields.

Conclusions

Women and children may be underappreciated as CL risk groups in agriculturally dependent regions. Despite the age-sex breakdown of clinical CL patients and high rates of deforestation occurring in the study area, transmission is mostly occurring outside of the largest population centers. Curbing transmission in non-domestic spaces may be limited to decreasing exposure to sandflies during the evening, nighttime, and early morning hours. Our paper serves as a cautionary tale for those relying solely on the demographic information obtained from clinic-based data to understand basic epidemiological trends of vector-borne infections.
Unexplained worsening of parkinsonian symptoms in a patient with advanced Parkinson’s disease as the sole initial presentation of COVID-19 infection: a case report
Authors: Kamel Walaa A. , Ismail Ismail Ibrahim , Ibrahim Mohamed , Al-Hashel Jasem Y.
Published: May 2021

Background

Parkinson’s disease (PD) is a neurodegenerative condition that has been reported following viral infections in rare occasions. Several neurological complications have emerged in association with coronavirus disease 2019 (COVID-19), since its declaration as a pandemic. Herein, we present a novel case of unexplained worsening of PD as the sole initial presentation of COVID-19, in the absence of fever or respiratory symptoms.

Case presentation

A 56-year-old male with advanced PD presented with severe rigidity, dystonic posturing of both feet, and confusion of 4 days duration. His condition progressed to an akinetic-rigid state and confusion during the following week, and a routine nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the 9th day of onset. He developed fever and dyspnea later and was intubated on the 10th day.

Conclusion

To our knowledge, worsening of PD symptoms as the sole initial manifestation of SARS-CoV-2 infection, in the absence of other cardinal features of COVID-19, has not been reported in the literature. We suggest testing for COVID-19 infection in patients with PD, especially advanced cases, who present with unexplained worsening of symptoms, even in the absence of COVID-19 cardinal features.