bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma
Authors: Wu Zhengyuan , Chen Leilei , Jin Chaojie , Xu Jing , Zhang Xingqun , Yao Yi
Published: October 2021

Background

Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear.

Methods

Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database.

Results

Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.
Analytical Study of Self-directed and Problem-Oriented Learning Sessions in Cardio-Respiratory Physiology
Authors: Palve Suchitra , Palve Sachin
Published: October 2021

Background: Learner-centred methods for teaching knowledge in the undergraduate medical curriculum utilizing an integrated approach include active learning approaches such as Problem-oriented learning and self-directed learning are two types of education.

Aim and objectives: The study aimed to see if self-directed learning and a problem-solving approach to physiology may benefit first-year medical students.

Material and methods: 250 students enrolled in Phase I MBBS for two physiology modules: CVS and RS, were involved in this cross-sectional study. Group A (n=125) received self-directed learning sessions for similar topics, whereas Group B (n=125) received problem-oriented learning sessions. An objective evaluation of all subjects covered was done after each SDL and POL session, and the results were analyzed using an unpaired t-test.

Results: Cardiovascular physiology self-directed learning sessions, 25.6 % (32/125) of students received maximum scores (group A), whereas 21.6 % (27/125) received moderate grades. 31.2 % (39/125) of problem-oriented sessions received maximum points, whereas 47.2 % (59/125) of pulmonary system module (group A) sig. SDL sessions received intermediate points. The p values (n=0.008) (n=0.009) for both modules indicated a significant difference between 32.8 % (41/125) of those who earned maximum scores and 48 % (60/125) of those who received intermediate grades. With p values of 0.0192, 0.0190, and 0.01179, respectively, pupils achieving 80–89 %, and 70–79 % in both SDL and PBL, had significant variations in their total scores in their internal evaluation when SDL and POL were compared to their overall scores.

Conclusion: Self-directed learning sessions are less successful than problem-oriented learning sessions at communicating concepts. It takes time to raise learner’s awareness and prepare them for active; Techniques for learning that are centered.
Assessment of Vitamin B12 Deficiency Caused by Metformin in Type II Diabetic Patients
Authors: Arun R.
Published: October 2021

Metformin use over time reduces vitamin B12 levels, according to several studies, and its clinical manifestation can be mistaken as diabetic peripheral neuropathy. In order to investigate vitamin-B12 deficiency in type II diabetic patients with long-term metformin treatment, a link between vitamin B12 and peripheral neuropathy, and to evaluate the quality of life in (T2DM) patients, the current study was done. At Sree Balaji Medical College and Hospital's outpatient and inpatient departments, a prospective observational case-control research was done. The study included 35 healthy volunteers (controls) and 35 Type 2 diabetes patients who had been on metformin for more than six months (cases). Patients' venous blood samples were collected in K2 EDTA vacutainers and centrifuged at 1500 rpm for 10 minutes, settled plasma was transferred into cryo-vials, and parameters such as Vitamin-B12, HbA1c, and CBP were estimated and this is used to conduct the statistical analysis. The prevalence of blood vitamin B12 deficiency and borderline deficiency in T2DM patients is 20.5 percent, while the mean HbA1C values in our study T2DM subjects are 9.07 percent, indicating either poor diabetes control or poor metformin drug compliance. Vitamin B12 insufficiency was found in 83 percent of T2DM patients who had been using metformin for 1 to 10 years. The reliability test was used to assess their quality of life, and the results revealed that the study participants' quality of life was poor.
Nutritional Status of Adolescent Girls in Corporation Schools in India: Still the Goal is Far Ahead
Authors: Kulkarni Priya , Jadhav Archana , Bhawalkar Jitendra
Published: October 2021

Adolescence is a vulnerable period for the incidence of malnutrition, as rapid growth takes place in this phase of life. Malnutrition, especially among adolescent girls, adversely affects future generations and indirectly impedes national productivity. Maternal malnutrition also contributes significantly to maternal mortality. It is required to be reduced to 70 per lac live births in 2030 from 167 per lac live births in 2013 to achieve sustainable development goals. The other crucial sustainable development goal is improvement in nutritional status in all phases of life. In the present study, we assessed the healthy situation by Body mass index and Haemoglobin estimation of adolescent girls incorporation school located at Pimpri, Pune, India. Most of the girls belonged to lower-middle to middle socioeconomic status. 67.9% of AGs under study were malnourished, while 8.6% were overweight. Only 3.5% of them had Haemoglobin in the normal range, 1% had severe, 65% of adolescent girls understudy had moderate anemia, and the rest had mild anemia. Results of the study show that India is still far away from attaining Sustainable development goals regarding the nutrition of adolescent girls and will have to take great efforts by existing program evaluation, modification, and strict implementation.
Understanding the Pathophysiology of Tourette’s Syndrome: A Review
Authors: Guha Ritu P. , Dhall Manish , Lather Prity , Singh Kulwant , Kadian Renu , Arya Ashwani
Published: October 2021

Tourette’s syndrome (TS) is a neuropsychiatric and neurodevelopment disease typified by deterioration of motor and vocal tics which leads to neuropsychiatric symptoms and impaired motor activities manifestation. Several lines of study indicate the interplay of genetic and environmental factors to be involved in this complex neuropsychiatric syndrome. Approximately 1% people are affected worldwide from this syndrome. In this review, a concise outline presented on the classification, its clinical features and neuropsychiatric co-morbidities linked with this syndrome. This paper also highlights the neurochemistry, dysfunction of (Cortioc-Striato-Thalamo-Cortical) CSTC circuits in TS and an overview on the management approach towards the prevention of TS. Regardless of the major improvements in the understanding of exact cellular and molecular basis of TS, the various evidence indicate that the various neurotransmitter such as dopamine, glutamate, gamma- aminobutyric acid (GABA), serotonin, noradrenergic, cholinergic system, serotonergic system and histaminergic pathways play a major role in pathogenesis of TS. Several research indicates that the dysfunction of CSTS circuits occurred in this complex syndrome These areas of research have contributed to the therapeutic approach towards the management of TS and also provide the basis for future progress of the therapeutic strategies. Thus, tics generated in TS, which affect the social and academic life of patients and disruptive or troubling the family of patients. Patients existing with this syndrome have to face difficulties integrating into social life and coping with day to day basis activities, as a consequence of the syndrome.
Structures and Materials in Stretchable Electroluminescent Devices
Authors: Yin Hexing , Zhu Yuan , Youssef Kareem , Yu Zhibin , Pei Qibing
Published: October 2021

Stretchable electroluminescent (EL) devices are obtained by partitioning a large emission area into areas specifically for stretching and light‐emission (island–bridge structure). Buckled and textile structures are also shown effective to combine the conventional light emitting diode fabrication with elastic substrates for structure‐enabled stretchable EL devices. Meanwhile, intrinsically stretchable EL devices which are characterized with uniform stretchability down to microscopic scale are relatively less developed but promise simpler device structure and higher impact resistance. The challenges in fabricating intrinsically stretchable EL devices with high and robust performance are in many facets, including stretchable conductors, emissive materials, and compatible processes. For the stretchable transparent electrode, ionically conductive gel, conductive polymer coating, and conductor network in surface of elastomer are all proven useful. The stretchable EL materials are currently limited to conjugated polymers, conjugated polymers with surfactants and ionic conductors added to boost stretchability, and phosphor particles embedded in elastomer matrices. These emissive materials operate under different mechanisms, require different electrode materials and fabrication processes, and the corresponding EL devices face distinctive challenges. This review aims to provide a basic understanding of the materials meeting both the mechanical and electronic requirements and important techniques to fabricate the stretchable EL devices.
Sensitivity to the communicative partner's attentional state: A developmental study on mother–infant dyads in wild chimpanzees (Pan troglodytes schweinfurthii)
Authors: Dafreville Mawa , Hobaiter Catherine , Guidetti Michèle , Sillam‐Dussès David , Bourjade Marie
Published: October 2021

Gestural communication permeates all domains of chimpanzees' social life and is intentional in use. However, we still have only limited information on how young apes develop the sociocognitive skills needed for intentional communication. In this cross‐sectional study, we document the development of behavioral adjustment to the recipient's visual attention—considered a hallmark of intentional communication—in wild immature chimpanzees' gestural communication. We studied 11 immature chimpanzees (Pan troglodytes schweinfurthii): three infants, four juveniles, and four adolescents gesturing towards their mother. We quantified silent‐visual, audible, and contact gestures indexed to maternal visual attention and inattention. We investigated unimodal adjustment, defined by the capacity of young chimpanzees to deploy fewer silent‐visual signals when their mothers did not show full visual attention towards them as compared with when they did. We then examined cross‐modal adjustment, defined as the capacity of chimpanzees to deploy more audible‐or‐contact gestures than silent‐visual gestures in the condition where their mothers did not show full visual attention as compared to when they did. Our results show a gradual decline in the use of silent‐visual gestures when the mother is not visually attentive with increasing age. The absence of silent‐visual gesture production toward a visually inattentive recipient (complete unimodal adjustment) was not fully in place until adolescence. Immature chimpanzees used more audible‐or‐contact gestures than silent‐visual ones when their mothers did not show visual attention and vice‐versa when they did. This cross‐modal adjustment was expressed in juveniles and adolescents but not in infants. Overall, this study shows that infant chimpanzees were limited in their sensitivity to maternal attention when gesturing, whereas adolescent chimpanzees adjusted their communication appropriately. Juveniles present an intermediate pattern with cross‐modal adjustment preceding unimodal adjustment and with variability in the age of onset.
Atomic Level Insights into Metal Halide Perovskite Materials by Scanning Tunneling Microscopy and Spectroscopy
Authors: Zhang Wei , Ono Luis K. , Xue Jiamin , Qi Yabing
Published: October 2021

Metal halide perovskite materials (MHPMs) have attracted significant attention because of their superior optoelectronic properties and versatile applications. The power conversion efficiency of MHPM solar cells (PSCs) has skyrocketed to 25.5 %. Although the performance of PSCs is already competitive, several important challenges still need to be solved to realize commercial applications. A thorough understanding of surface atomic structures and structure–property relationships is at the heart of these remaining issues. Scanning tunneling microscopy (STM) and spectroscopy (STS) can be used to characterize the surface properties of MHPMs, which can offer crucial insights into MHPMs at the atomic scale. This Review summarizes recent progress in STM and STS studies on MHPMs, with a focus on the surface properties. We provide understanding from the comparative perspective of several different MHPMs. We also highlight a series of novel phenomena observed by STM and STS. Finally, we outline a few research topics of primary importance for future studies.
The interplay of protein engineering and glycoengineering to fine‐tune antibody glycosylation and its impact on effector functions
Authors: Wang Qiong , Wang Tiexin , Zhang Roushu , Yang Shuang , McFarland Kevin S. , Chung Cheng‐Yu , Jia Hongpeng , Wang Lai‐Xi , Cipollo John F. , Betenbaugh Michael J.
Published: October 2021

The N‐glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function. For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied. Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α‐2,6‐sialylated (ST6KI), and defucosylated α‐2,6‐sialylated (FUT8KOST6KI), expressing either a wild‐type anti‐CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant. Matrix‐assisted laser desorption ionization‐time of flight mass spectrometry characterization of antibody N‐glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching. Furthermore, overexpression of recombinant human α‐2,6‐sialyltransferase resulted in a predominance of α‐2,6‐sialylation rather than α‐2,3‐sialylation for both WT and heavily sialylated F241A antibody N‐glycans. Interestingly, knocking out α‐1,6‐fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N‐glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody. Further complement‐dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants. However, the FUT8KO WT antibody, with a large fraction of bi‐GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples. Furthermore, for the F241A mutants, a higher CDC activity was observed for α‐2,6‐ compared to α‐2,3‐sialylation. Antibody‐dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution. Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result. This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
Migrasomes and exosomes; different types of messaging vesicles in podocytes
Authors: Ardalan Mohammadreza , Hosseiniyan Khatibi Seyed Mahdi , Rahbar Saadat Yalda , Bastami Milad , Nariman‐Saleh‐Fam Ziba , Abediazar Sima , Khalilov Rovshan , Zununi Vahed Sepideh
Published: October 2021

Podocytes, highly specified kidney epithelial cells, live under several pathological stimuli and stresses during which they adapt themselves to keep homeostasis. Nevertheless, under extreme stress, a complex scenario of podocyte damage and its consequences occur. Podocyte damage causes foot process effacement and their detachment from the glomerular basement membrane, leading to proteinuria. Podocyte‐derived extracellular vesicles (pEVs), mainly microparticles and exosomes are considered as signaling mediators of intercellular communication. Recently, it has been shown that throughout the injury‐related migration procedure, podocytes are capable of releasing the injury‐related migrasomes. Evidence indicates that at the early stages of glomerular disorders, increased levels of pEVs are observed in urine. At the early stage of nephropathy, pEVs especially migrasomes seem to be more sensitive and reliable indicators of podocyte stress and/or damage than proteinuria. This review highlights the current knowledge of pEVs and their values for the diagnosis of different kidney diseases.
Malignant melanoma of parotid glands from a neglected lesion: A case report
Authors: Ahadi Mahsa , Rakhshan Azadeh , Mousavi Seyed Reza , Saebnoori Homeira
Published: October 2021

Observing a metastatic malignant melanoma and its primary lesion at the same time is rare. The histopathological detection of any unusual pigmented lesion is critical.
Erythema Multiforme Major following SARS‐CoV‐2 vaccine
Authors: Saibene Alberto Maria , Alliata Andrea , Cozzi Anna Teresa , Ottavi Alice , Spagnolini Sofia , Pipolo Carlotta , Maccari Alberto , Felisati Giovanni
Published: October 2021

Erythema multiforme major, an immune‐mediated skin reaction to infections or medications with oral involvement, should be taken into account as a potential side effect of several vaccines, including SARS‐CoV‐2. Correct patient history collection allows prompt recognition and subsequent successful medical management with oral corticosteroids.
Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system
Authors: Gritsch Simon , Batchelor Tracy T. , Gonzalez Castro L. Nicolas
Published: October 2021

The 2016 revised fourth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporated molecular features with histologic grading, revolutionizing how oncologists conceptualize primary brain and spinal cord tumors as well as providing new insights into their management and prognosis. The 2021 revised fifth edition of the WHO classification further integrates molecular alterations for CNS tumor categorization, updating current understanding of the pathophysiology of many of these disease entities. Here, the authors review changes in the new classification for the most common primary adult tumors—gliomas (including astrocytomas, oligodendrogliomas, and ependymomas) and meningiomas—highlighting the key genomic alterations for each group classification to help clinicians interpret them as they consider therapeutic options—including clinical trials and targeted therapies—and discuss the prognosis of these tumors with their patients. The revised, updated 2021 WHO classification also further integrates molecular alterations in the classification of pediatric CNS tumors, but those are not covered in the current review.
Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia
Authors: Aldoss Ibrahim , Otoukesh Salman , Zhang Jianying , Mokhtari Sally , Ngo Dat , Mojtahedzadeh Mona , Al Malki Monzr M. , Salhotra Amandeep , Ali Haris , Aribi Ahmed , Sandhu Karamjeet S. , Arslan Shukaib , Koller Paul , Ball Brian , Stewart Forrest , Curtin Peter , Artz Andrew , Nakamura Ryotaro , Marcucci Guido , Forman Stephen J. , Stein Anthony S. , Pullarkat Vinod
Published: October 2021

Background

Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease–positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19– disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood.

Methods

This study retrospectively reviewed the outcomes of adult patients with B‐cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013‐2021) and analyzed factors associated with treatment response and EMD failure.

Results

The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD.

Conclusions

A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure.

Lay Summary

Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia.

A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites.

Most extramedullary failure cases retain CD19 expression.
Process based volatile memory forensics for ransomware detection
Authors: Arfeen Asad , Asim Khan Muhammad , Zafar Obad , Ahsan Usama
Published: October 2021

Ransomware is an emerging category of malware that locks computer data via powerful cryptographic algorithms. The global propagation of ransomware is a serious threat for individuals and organizations. The banking sector and financial institutions are the prime targets of such ransomware attacks. In case of such an attack, the field of digital forensics helps in estimation of the severity and data loss caused by the attack. Traditional digital forensics investigations make use of static or behavioral analysis to detect malware in infected systems. However, these procedures are challenged by malware obfuscation techniques. Malicious processes can stay inactive and undetected if only a single memory dump is analyzed. Thus, there is a need to collect numerous memory dumps of an individual program that can help with comprehensive and accurate analysis. In this article, we have developed a framework for volatile memory acquisition at regular time intervals to analyze the behavior of individual processes in memory. Through memory forensics, salient features are extracted from the infected memory dumps. These features can be utilized to classify malicious and benign processes efficiently through machine learning as compared to conventional techniques.
Water‐Mediated Thermal Rearrangement of a Cage‐Opened C60 Derivative
Authors: Hashikawa Yoshifumi , Murata Yasujiro
Published: October 2021

The partial zipping of a fullerene orifice was achieved by a water‐mediated thermal rearrangement at 150 °C for one day while the orifice size changed from 16‐ to 14‐membered ring with the generation of a fused pentagon. The addition of B(C6F5)3 was found to facilitate the reaction likely due to the coordination to carbonyl groups on the orifice. By extending the reaction time, the decarbonylation took place to give another 14‐membered‐ring orifice where the Michael addition of water occurred under acidic conditions. The computational study suggested that the formation of a carboxylic acid and Fischer‐type carbene plays a key role in the C−C bond cleavage/reformation processes during the rearrangement.
Multi‐proxy approach of the stratigraphy, geochemistry, and sedimentology of Eocene Margalla Hill Limestone: Case study from Muzaffarabad area, Sub‐Himalayas, Pakistan
Authors: Shahzad Amir , Munir Munir ul Hassan , Adatte Thierry , Riaz Muhammad Tayyib , Basharat Muhammad , Ahmed Khawaja Shoaib , Sarfraz Yasir , Khan Jahanzeb , Mughal Muhammad Saleem
Published: October 2021

To investigate the sedimentological characteristics of the Margalla Hill Limestone (MHL), a multi‐proxy approach including geochemical, mineralogical, and micropalaeontological investigations were carried out. Using detailed field observations and petrographic investigation of the studied section, five microfacies were dentified. Total organic carbon (TOC) values of the limestone are generally low (0.10–0.96%) and highly degraded, as observed from the low hydrogen index (i.e., 17–349 mg HC/g TOC). TOC is mainly Type‐III and Type‐IV organic matter that reflects a continental source or highly weathered marine organic matter (OM) with minor Type‐II which corresponds to algal or bacterial OM. The values of Tmax range from 419 to 512°C for most of the samples, which lies within the mature stage. Major element abundances do not vary significantly in the studied unit and are mainly linked to variations in clay contents. Trace elements (V, Cr, Mn, Zn, Ni, Cu, Th, Rb, U, and Zr) of the MHL depict a mainly detrital origin for shales, and overall decrease in trace element's concentration suggests a change from physical to chemical weathering. The rate of sedimentation as determined by the Th/U ratio indicates a regular to irregular low rate of sedimentation, from base to top of the studied section. The redox conditions, as reflected in the variation of Cr (V/Cr), using the V/Cr ratio with Ni + V indicate that the MHL was deposited under oxic‐dysoxic conditions. Chemical Index of Alteration, Chemical Index of Weathering, Plagioclase Index of Alteration, and Weathering Index of Parker showed that the source region was subjected to intense chemical weathering likely under tropical palaeoclimatic conditions with abundant rainfall. The limestone consists mainly of calcite followed by minor quartz and dolomite. Clay mineralogy revealed that the clay fraction is dominated by kaolinite, smectite, mica, and chlorite. The microfossils of various genera of benthic foraminifera have been identified. Based on benthic foraminifera, an Early Eocene (SBZ‐8; Middle Ilrdian 2) age has been assigned to the MHL.
Strategies for implementing music‐based interventions for people with dementia in long‐term care facilities: A systematic review
Authors: Amano Takashi , Hooley Cole , Strong Joe , Inoue Megumi
Published: October 2021

Objectives

Research has found that music‐based interventions can decrease behavioral and psychological symptoms of dementia or behaviors that challenge (BPSD/BtC). However, how to effectively implement these interventions is unclear. This study synthesizes available evidence regarding implementation strategies and outcomes of music‐based interventions for people with dementia at residential long‐term care facilities.

Methods

Study registered with PROSPERO (registration number: CRD42020194354). We searched the following databases: PsychInfo, PubMed, MEDLINE, CINAHL, and The Cochrane Library. Inclusion criteria included articles targeting music‐based interventions conducted for people with dementia, studies conducted in residential long‐term care facilities, and articles that reported implementation strategies and outcomes of the intervention.

Results

Of the included eight studies, half were studies of music therapy and the other half were on individualized music. 49 implementation strategies were reported. The most frequently reported category of strategies was planning (34.7%), followed by education (24.5%), quality management (24.5%), restructuring (12.2%), and finance (4.1%). No strategies under the category of attending to the policy context were reported. The most frequently reported implementation outcomes were appropriateness (27.3%), followed by adoption (22.7%), fidelity (22.7%), acceptability (9.1%), sustainability (9.1%), and cost (9.1%). No studies measured feasibility or penetration.

Conclusions

Although various effective implementation strategies were identified, we were unable to examine the effectiveness of individual implementation strategies due to the designs of the selected studies. Less attention has been paid to strategies that aim at structural changes of intervention delivery systems. Future studies should investigate facilitators and barriers of implementing music‐based interventions especially focusing on structural aspects.
A novel cyclic NP1 reveals obstruction of EGFR kinase activity and attenuation of EGFR‐driven cell lines
Authors: Jiwacharoenchai Nattanan , Tabtimmai Lueacha , Kiriwan Duangnapa , Suwattanasophon Chonticha , Seetaha Supaphorn , Sinthuvanich Chomdao , Choowongkomon Kiattawee
Published: October 2021

Aberrations of the epidermal growth factor receptor (EGFR), for example, mutations and overexpression, play pivotal roles in various cellular functions, such as proliferation, migration, and cell differentiation. Approved small molecule‐based inhibitors, including gefitinib and erlotinib, are used clinically to target the tyrosine kinase domain of EGFR (TK‐EGFR). However, the severity of the side effects, off‐target effects, and drug resistance is a concern. Cyclic peptides are a well‐known peptide format with high stability and are promising molecules for drug development. Herein, the Ph.D.™‐C7C phage display library was used to screen cyclic peptides against TK‐EGFR. Biopanning, both with and without propagation methods, was performed to assess the highest capacity peptides using the enzymatic activity of TK‐EGFR. Interestingly, NP1, a peptide selected during biopanning without propagation demonstrated an inhibitory effect against TK‐EGFR at IC50 within the nanomolar range; this effect was better than that of P1 obtained using biopanning with propagation. Moreover, NP1 elicited EGFR with an affinity binding (KD) value of 18.40 ± 5.50 µM by surface plasmon resonance (SPR). Introducing cell‐penetrating peptides or Arginine‐9 (Arg9) at the N‐terminus of NP1 thus improves cell‐penetrability and can lead to the inhibition of EGFR‐driven cancer cell lines; however, it exhibits no hepatotoxicity. Furthermore, NP1 caused a decrease in phosphorylated EGFR after activation within cells. A docking model shows that NP1 interacted primarily with TK‐EGFR via hydrogen bonding. Together, this suggests that NP1 is a novel EGFR peptide inhibitor candidate with specificity and selectivity toward TK‐EGFR, and may be applied to targeted therapy.
The occurrence of COVID‐19 is associated with air quality and relative humidity
Authors: Tong Ling , Ji Lu , Li Dan , Xu Huihui
Published: October 2021

The association between meteorological factors and COVID‐19 is important for the prevention and control of COVID‐19. However, similar studies are relatively rare in China. This study aims to investigate the association between COVID‐19 and meteorological factors, such as average temperature, relative humidity, and air quality index (AQI), and average wind speed. We collected the daily confirmed cases of COVID‐19 and meteorological factors in Shanghai China from January 10, 2020 to March 31, 2020. A generalized additive model was fitted to quantify the associations between meteorological factors and COVID‐19 during the study period. A negative association between average temperature and daily confirmed cases of COVID‐19 was found on lag 13 days. In addition, we observed a significant positive correlation between meteorological factors (AQI, relative humidity) and daily confirmed cases of COVID‐19. A 10 increase in AQI (lag1/7/8/9/10 days) was correlated with a 4.2%–9.0% increase in the daily confirmed cases of COVID‐19. A 1% increase in relative humidity (lag1/4/7/8/9/10 days) was correlated with 1.7%–3.7% increase in the daily confirmed cases of COVID‐19. However, the associations between average wind speed and the daily confirmed cases of COVID‐19 is complex in different lag days. In summary, meteorological factors could affect the occurrence of COVID‐19. Reducing the effects of meteorological factors on COVID‐19 may be an important public health action for the prevention and control of COVID‐19.
Insights into Holocene relative sea‐level changes in the southern North Sea using an improved microfauna‐based transfer function
Authors: Scheder Juliane , Bungenstock Friederike , Haynert Kristin , Pint Anna , Schlütz Frank , Frenzel Peter , Wehrmann Achim , Brückner Helmut , Engel Max
Published: October 2021

In light of global warming and rising relative sea level (RSL), detailed reconstructions of RSL histories and their controlling processes are essential in order to manage coastal‐protection challenges. This study contributes to unravelling Holocene RSL change on the East Frisian North Sea coast in high resolution and with a new approach for the German Bight. For the first time, a transfer function (vertical error: 29.7 cm ≙ ~11% of the mean tidal range) for RSL change based on a combined training set of benthic foraminifers and ostracods from the back‐barrier tidal basin of Spiekeroog is applied to the Holocene record of the back‐barrier tidal basin of Norderney. The resulting RSL curve for the Norderney tidal basin is corrected for decompaction and shows a deceleration in RSL rise between 6000 and 5000 cal bp.The smallest possible error envelope (~1 m) results from the good suitability of salt‐marsh layers between 5000 and 4000 cal bp.The RSL curve provides an approach towards the closure of the common data gap of peat‐based curves for the southern North Sea related to a lack of basal peats in the youngest age range, and verifies regional differences in glacial isostatic adjustment.
Improving dermal level images from reflectance confocal microscopy using wavelet‐based transformations and adaptive histogram equalization
Authors: Hanlon Katharine L. , Wei Grace , Braue Jonathan , Correa‐Selm Lilia , Grichnik James M.
Published: October 2021

Objectives

Reflectance confocal microscopy (RCM) generates scalar image data from serial depths in the skin, allowing in vivo examination of cellular features. The maximum imaging depth of RCM is approximately 250 µm, to the papillary dermis, or upper reticular dermis. Frequently, important diagnostic features are present in the dermis, hence improved visualization of deeper levels is advantageous.

Methods

Low contrast and noise in dermal images were improved by employing a combination of wavelet‐based transformations and contrast‐limited adaptive histogram equalization.

Results

Preserved details, noise reduction, increased contrast, and feature enhancement were observed in the resulting processed images.

Conclusions

Complex and combined wavelet‐based enhancement approaches for dermal level images yielded reconstructions of higher quality than less sophisticated histogram‐based strategies. Image optimization may improve the diagnostic accuracy of RCM, especially for entities with dermal findings.
A Novel Variant of ATP5MC3 Associated with Both Dystonia and Spastic Paraplegia
Authors: Neilson Derek E. , Zech Michael , Hufnagel Robert B. , Slone Jesse , Wang Xinjian , Homan Shelli , Gutzwiller Lisa M. , Leslie Elizabeth J. , Leslie Nancy D. , Xiao Jianfeng , Hedera Peter , LeDoux Mark S. , Gebelein Brian , Wilbert Friederike , Eckenweiler Matthias , Winkelmann Juliane , Gilbert Donald L. , Huang Taosheng
Published: October 2021

Background

In a large pedigree with an unusual phenotype of spastic paraplegia or dystonia and autosomal dominant inheritance, linkage analysis previously mapped the disease to chromosome 2q24‐2q31.

Objective

The aim of this study is to identify the genetic cause and molecular basis of an unusual autosomal dominant spastic paraplegia and dystonia.

Methods

Whole exome sequencing following linkage analysis was used to identify the genetic cause in a large family. Cosegregation analysis was also performed. An additional 384 individuals with spastic paraplegia or dystonia were screened for pathogenic sequence variants in the adenosine triphosphate (ATP) synthase membrane subunit C locus 3 gene (ATP5MC3). The identified variant was submitted to the “GeneMatcher” program for recruitment of additional subjects. Mitochondrial functions were analyzed in patient‐derived fibroblast cell lines. Transgenic Drosophila carrying mutants were studied for movement behavior and mitochondrial function.

Results

Exome analysis revealed a variant (c.318C > G; p.Asn106Lys) (NM_001689.4) in ATP5MC3 in a large family with autosomal dominant spastic paraplegia and dystonia that cosegregated with affected individuals. No variants were identified in an additional 384 individuals with spastic paraplegia or dystonia. GeneMatcher identified an individual with the same genetic change, acquired de novo, who manifested upper‐limb dystonia. Patient fibroblast studies showed impaired complex V activity, ATP generation, and oxygen consumption. Drosophila carrying orthologous mutations also exhibited impaired mitochondrial function and displayed reduced mobility.

Conclusion

A unique form of familial spastic paraplegia and dystonia is associated with a heterozygous ATP5MC3 variant that also reduces mitochondrial complex V activity.
Development of a Novel Pharmacophore Model Guided by the Ensemble of Waters and Small Molecule Fragments Bound to SARS‐CoV‐2 Main Protease
Authors: Kumar Pawan , Mohanty Debasisa
Published: October 2021

Recent fragment‐based drug design efforts have generated huge amounts of information on water and small molecule fragment binding sites on SARS‐CoV‐2 Mpro and preference of the sites for various types of chemical moieties. However, this information has not been effectively utilized to develop automated tools for in silico drug discovery which are routinely used for screening large compound libraries. Utilization of this information in the development of pharmacophore models can help in bridging this gap. In this study, information on water and small molecule fragments bound to Mpro has been utilized to develop a novel Water Pharmacophore (Waterphore) model. The Waterphore model can also implicitly represent the conformational flexibilities of binding pockets in terms of pharmacophore features. The Waterphore model derived from 173 apo‐ or small molecule fragment‐bound structures of Mpro has been validated by using a dataset of 68 known bioactive inhibitors and 78 crystal structure bound inhibitors of SARS‐CoV‐2 Mpro. It is encouraging to note that, even though no inhibitor data has been used in developing the Waterphore model, it could successfully identify the known inhibitors from a library of decoys with a ROC‐AUC of 0.81 and active hit rate (AHR) of 70 %. The Waterphore model is also general enough for potential applications for other drug targets.
Thermogravitational convection of power‐law nanofluid in a cavity with a heat‐generated section on the bottom wall
Authors: Loenko Darya S. , Shenoy Aroon , Sheremet Mikhail A.
Published: October 2021

Optimization of cooling systems for electronic devices is one of the crucial challenges in the modern engineering world. Inclusion of nanosized particles to working heat transfer liquids can enhance the heat removal from the heated elements in electronics. Taking into account these data, the present research is devoted to numerical analysis of natural convection in a cavity filled with a non‐Newtonian nanosuspension under an influence of a heat‐generating wall section. The paper contains the simulation outcomes for two different cases, namely, a heat‐generating wall section with constant heat flux and a heat‐generating wall section with constant temperature. The considered phenomenon has been described using the single‐phase nanofluid model where the base liquid is a pseudoplastic fluid. The rheological parameters of the host liquid including the coefficient of flow density and an indicator of fluid behavior are the empirical data of MWCNT nanofluids. The non‐Newtonian nature of the nanoliquid has been described by the Ostwald‐de‐Waele power law. Detailed analysis has been carried out for different governing parameters including the Rayleigh number, the volume fraction of nanoparticles, and the size of the heater using the non‐primitive dimensionless variables and the finite difference method. Obtained results illustrate different temperature patterns for various boundary conditions. Moreover, in the case of heat‐generating element, the average Nusselt number is greater than for the isothermal heater. It should be noted that the considered nanofluid model reflects the energy transference degradation with a growth of the nanoparticles concentration.
Nanopore sensing of γ‐cyclodextrin induced host‐guest interaction to reverse the binding of perfluorooctanoic acid to human serum albumin
Authors: Wei Xiaojun , Wang Qian , Liu Chang
Published: October 2021

Perfluorooctanoic acid (PFOA) has been one of the most common perfluorochemicals, which are globally pervasive contaminants that are persistent, bioaccumulative, toxic, and have adverse impacts on human health. The highest concentration of PFOA occurs in the blood, where it strongly binds to human serum albumins (HSA). Thus, a method to reverse the HSA‐PFOA binding is critical to help facilitate the faster elimination of PFOA from the body to minimize its toxicological effects. Inspired by the remediation effect of cyclodextrin (CD) to PFOA through host‐guest interactions, herein, by elucidating inter‐molecular interactions using a nanopore sensor, we demonstrated in vitro reversal of the binding of PFOA to HSA using γ‐cyclodextrin (γ‐CD). The competition behavior for the complexation of PFOA between HSA and γ‐CD was discussed in combination with in situ nanopore current recording and nuclear magnetic resonance (NMR) characterization. The present work not only demonstrates the potential therapeutic application of γ‐CD for PFOA removal from human blood, but also provides an emerging method for investigating interactions between organic compounds and proteins.
Viruses and Mycoplasma pneumoniae are the main etiological agents of community‐acquired pneumonia in hospitalized pediatric patients in Spain
Authors: Otheo Enrique , Rodríguez Mario , Moraleda Cinta , Domínguez‐Rodríguez Sara , Martín María D. , Herreros María L. , Vázquez Carmen , Folgueira María D. , Pérez‐Rivilla Alfredo , Jensen Julia , López Agustín , Berzosa Arantxa , Sanz de Santaeufemia Francisco J. , Jiménez Ana B. , Sainz Talía , Llorente Marta , Santos Mar , Garrote Elisa , Muñoz Cristina , Sánchez Paula , Illán Marta , Coca Ana , Barrios Ana , Pacheco Mónica , Arquero Carmen , Gutiérrez Lourdes , Epalza Cristina , Rojo Pablo , Serna‐Pascual Miquel , Mota Inmaculada , Moreno Santiago , Galán Juan C. , Tagarro Alfredo ,   VALS‐DANCE and PCAPE Working Groups
Published: October 2021

Objectives

To describe the etiology of community‐acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology.

Hypothesis

The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data.

Design

Observational, multicenter, and prospective study.

Patient selection

This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019.

Methods

An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups.

Results

Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para‐pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens.

Conclusions

Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient.