bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous manipulation of multiple genes within a same regulatory stage for iterative evolution of Trichoderma reesei
Authors: Sun Xianhua , Liang Yazhe , Wang Yuan , Zhang Honglian , Zhao Tong , Yao Bin , Luo Huiying , Huang Huoqing , Su Xiaoyun 
Published: March 2022

Abstract
Background
While there is growing interest in developing non-canonical filamentous fungi as hosts for producing secretory proteins, genetic engineering of filamentous fungi for improved expression often relies heavily on the understanding of regulatory mechanisms.

Results
In this study, using the cellulase-producing filamentous fungus Trichoderma reesei as a model system, we designed a semi-rational strategy by arbitrarily dividing the regulation of cellulase production into three main stages-transcription, secretion, and cell metabolism. Selected regulatory or functional genes that had been experimentally verified or predicted to enhance cellulase production were overexpressed using strong inducible or constitutive promoters, while those that would inhibit cellulase production were repressed via RNAi-mediated gene silencing. A T. reesei strain expressing the surface-displayed DsRed fluorescent protein was used as the recipient strain. After three consecutive rounds of engineering, the cellulase activity increased to up to 4.35-fold and the protein concentration increased to up to 2.97-fold in the genetically modified strain.

Conclusions
We demonstrated that, as a proof-of-concept, selected regulatory or functional genes within an arbitrarily defined stage could be pooled to stimulate secretory cellulase production, and moreover, this method could be iteratively used for further improvement. This method is semi-rational and can essentially be used in filamentous fungi with little regulatory information.
Echinococcus spp. and genotypes infecting humans in Tibet Autonomous Region of China: a molecular investigation with near-complete/complete mitochondrial sequences
Authors: Zhao Yanping , Gesang Dunzhu , Wan Li , Li Jiandong , Qiangba Gezhen , Danzeng Wangmu , Basang Zhuoga , Renzhen Nibu , Yin Jiefang , Gongsang Quzhen , Cai Huimin , Pang Huasheng , Wang Daxi , Asan  , Zhang Qingda , Li Junhua , Chen Weijun 
Published: March 2022

Abstract
Background
Molecular markers are essential to identify Echinococcus species and genotypes in areas with multiple Echinococcus species to understand their epidemiology and pathology. Tibet Autonomous Region (TAR) is one of the areas worst hit by echinococcosis. However, molecular epidemiology is still missing among echinococcosis patients in TAR. This research explored the Echinococcus species and genotypes infecting humans in TAR and the population diversity and the possible origin of G1 in TAR.

Methods
Cyst samples were collected in one echinococcosis-designated hospital in TAR. Echinococcus species and genotypes were identified through a maximum-likelihood approach with near-complete/complete mtDNA using IQ-TREE. Phylogenetic networks were built with PopART, and the phylogeographical diffusion pattern was identified using a Bayesian discrete phylogeographic method.

Results
Using phylogenetic trees made with near-complete/complete mtDNA obtained from 92 cysts from TAR patients, the Echinococcus species and genotypes infecting humans in TAR were identified as Echinococcus granulosus (s.s.) G1 (81, 88.04%), accounting for the majority, followed by G6 of the E. canadensis cluster (6, 6.52%), E. granulosus (s.s.) G3 (3, 3.26%), and E. multilocularis (2, 2.17%). An expansion trend and a possible recent bottleneck event were confirmed among the G1 samples in TAR. Adding the other near-complete mtDNA of G1 samples globally from the literature, we identified the possible phylogeographic origin of the G1 samples in TAR as Turkey.

Conclusions
Using near-complete/complete mtDNA sequences of Echinococcus spp. obtained from echinococcosis patients, a variety of Echinococcus species and genotypes infecting humans throughout TAR were identified. As far as we know, this is the first comprehensive molecular investigation of Echinococcus species and genotypes infecting humans throughout TAR. We identified, for the first time to our knowledge, the possible origin of the G1 in TAR. We also enriched the long mtDNA database of Echinococcus spp. and added two complete E. multilocularis mtDNA sequences from human patients. These findings will improve our knowledge of echinococcosis, help to refine the targeted echinococcosis control measures, and serve as a valuable baseline for monitoring the Echinococcus species and genotypes mutations and trends of the Echinococcus spp. population in TAR.

Graphical Abstract
Phylogenetic relationship between the endosymbiont “Candidatus Riesia pediculicola” and its human louse host
Authors: Hammoud Alissa , Louni Meriem , Missé Dorothée , Cortaredona Sébastien , Fenollar Florence , Mediannikov Oleg 
Published: March 2022

Abstract
Background
The human louse (Pediculus humanus) is a haematophagous ectoparasite that is intimately related to its host. It has been of great public health concern throughout human history. This louse has been classified into six divergent mitochondrial clades (A, D, B, F, C and E). As with all haematophagous lice, P. humanus directly depends on the presence of a bacterial symbiont, known as “Candidatus Riesia pediculicola”, to complement their unbalanced diet. In this study, we evaluated the codivergence of human lice around the world and their endosymbiotic bacteria. Using molecular approaches, we targeted lice mitochondrial genes from the six diverged clades and Candidatus Riesia pediculicola housekeeping genes.

Methods
The mitochondrial cytochrome b gene (cytb) of lice was selected for molecular analysis, with the aim to identify louse clade. In parallel, we developed four PCR primer pairs targeting three housekeeping genes of Candidatus Riesia pediculicola: ftsZ, groEL and two regions of the rpoB gene (rpoB-1 and rpoB-2).

Results
The endosymbiont phylogeny perfectly mirrored the host insect phylogeny using the ftsZ and rpoB-2 genes, in addition to showing a significant co-phylogenetic congruence, suggesting a strict vertical transmission and a host–symbiont co-speciation following the evolutionary course of the human louse.

Conclusion
Our results unequivocally indicate that louse endosymbionts have experienced a similar co-evolutionary history and that the human louse clade can be determined by their endosymbiotic bacteria.

Graphical Abstract
Physiotherapy management of acute transverse myelitis in a pediatric patient in a Nigerian hospital: a case report
Authors: Onyekere Chukwuebuka P. , Igwesi-Chidobe Chinonso N. 
Published: March 2022

Abstract
Background
Transverse myelitis is a rare neurological disorder of the spinal cord, caused by inflammation and damage of the myelin sheath of the neurons of the spinal cord across one or more spinal segments. This causes a disruption in the passage of nervous signals leading to motor, sensory, and autonomic dysfunction. This affects the physical and psychological health, as well as the functional status of the patient. This case report presents the physiotherapy evaluation and management of acute transverse myelitis in a pediatric patient.

Case presentation
A 17-year-old Nigerian male diagnosed with acute transverse myelitis was referred to the physiotherapy team for expert management. The patient presented with severe muscle spasms and frequent jerking movements, shocking sensations, hypertonicity, and spasticity (modified Ashworth scale: 1+ on the right, > 2 on the right), and muscle strength of the lower limbs (Oxford muscle grading: 3/5 on the left, 1/5 on the left) with impaired functional status (Functional Independence Measure: 70/126).The patient tolerated and participated in the physiotherapy interventions (cryotherapy, soft tissue mobilization, splinting) and exercises (free active, resistance and functional exercises) in the ward and outpatient clinic, as well as subsequent home programmes (free active, resistance and functional exercises). The patient also received other medical and pharmacological interventions in the ward. After 23 days of therapy, the patient improved in all clinical outcomes, including muscle spasm and hypertonicity, spasticity (modified Ashworth scale: 0 bilaterally), sensation, and muscle strength (Oxford muscle grading: 5/5 bilaterally). The patient’s overall functional status also improved (Functional Independence Measure: 117/126).

Conclusions
Physiotherapy improved the symptoms of acute transverse myelitis in this patient. Randomized controlled trials are required to replicate these findings.
Patient engagement strategies for adults with chronic conditions: an evidence map
Authors: Aboumatar Hanan , Pitts Samantha , Sharma Ritu , Das Asar , Smith Brandon M. , Day Jeff , Holzhauer Katherine , Yang Sejean , Bass Eric B. , Bennett Wendy L. 
Published: March 2022

AbstractBackgroundPatient and family engagement (PFE) has been defined as a partnership between patients, families, and health care providers to achieve positive health care outcomes. There is evidence that PFE is critical to improving outcomes. We sought to systematically identify and map the evidence on PFE strategies for adults with chronic conditions and identify areas needing more research.MethodsWe searched PubMed, CINAHL, EMBASE, and Cochrane, January 2015 to September 2021 for systematic reviews on strategies for engaging patients with chronic conditions and their caregivers. From each review, we abstracted search dates, number and type of studies, populations, interventions, and outcomes. PFE strategies were categorized into direct patient care, health system, and community-policy level strategies. We found few systematic reviews on strategies at the health system, and none at the community-policy level. In view of this, we also searched for original studies that focused on PFE strategies at those two levels and reviewed the PFE strategies used and study findings.ResultsWe found 131 reviews of direct patient care strategies, 5 reviews of health system strategies, and no reviews of community-policy strategies. Four original studies addressed PFE at the health system or community-policy levels. Most direct patient care reviews focused on self-management support (SMS) (n= 85) and shared decision-making (SDM) (n= 43). Forty-nine reviews reported positive effects, 35 reported potential benefits, 37 reported unclear benefits, and 4 reported no benefits. Health system level strategies mainly involved patients and caregivers serving on advisory councils. PFE strategies with the strongest evidence focused on SMS particularly for patients with diabetes. Many SDM reviews reported potential benefits especially for patients with cancer.DiscussionMuch more evidence exists on the effects of direct patient care strategies on PFE than on the effects of health system or community-policy strategies. Most reviews indicated that direct patient care strategies had positive effects or potential benefits.A limitation of this evidence map is that due to its focus on reviews, which were plentiful, it did not capture details of individual interventions. Nevertheless, this evidence map should help to focus attention on gaps that require more research in efforts to improve PFE.
Mode-dependent delays for dissipative filtering of stochastic semi-Markovian jump for neural networks
Authors: Aslam Muhammad Shamrooz , Li Qianmu , Hou Jun , Qiulong Hua 
Published: March 2022

AbstractThis work is concerned with the issue of dissipative filtering for stochastic semi-Markovian jump via neural networks where the time-varying delay is based upon another semi-Markov process. Dissipative performance analysis is employed to solve a mode-dependent filtering problem in a unified way. To achieve this task, we implemented the recently proposed notion of extended dissipativity, which gives an inequality equivalent to the well-known $H_{\infty }$

H
∞

, $L_{2}$

L
2

–$L_{\infty }$

L
∞

, and dissipative performances. Different from the existing literature (Arslan et al. in Neural Netw 91:11–21, 2017; Chen et al. in ISA Trans. 101:170–176, 2020) where mostly delay-free filters have been investigated, our filter contains a communication delay. Based upon the delay-dependent conditions, for the analysis of stochastic stability and extended dissipativity for neural networks with time-varying delays, our results are obtained by using a mode-dependent Lyapunov–Krasovskii functional together with a novel integral inequality. Original stochastic filtering conditions are characterized by linear matrix inequalities. A numerical simulation is elaborated to elucidate the feasibility of the proposed design methodology.
Customer engagement design during the COVID 19 pandemic, mutual trust and intelligent automation: a conceptual perspective
Authors: Alfalih Abdullah Abdulmohsen 
Published: March 2022

AbstractThe adoption and use of artificial intelligence, and the application of this concept through the development and implementation of intelligent automation is not considered simply as an option, but rather as an obligation in current times, due to the considerable change caused by the COVID 19 pandemic and responses to it. This study is an attempt to more thoroughly understand and clarify how the adoption of such intelligent automation can work to improve customer engagement in the food and restaurant domain. To attend to this objective, a theoretical framework is developed and tested based on an integrative approach of determinants of customer engagement through artificial intelligence to increase trust levels when intelligent automation is used. This paper will contribute to the construction of a matrix of customer engagement based on the different steps identified in the customer engagement cycle, and build a co-constructive and dynamic model of customer engagement in relation to mutual’ trust and intelligent automation.
Artificial intelligence in diagnosis of knee osteoarthritis and prediction of arthroplasty outcomes: a review
Authors: Lee Lok Sze , Chan Ping Keung , Wen Chunyi , Fung Wing Chiu , Cheung Amy , Chan Vincent Wai Kwan , Cheung Man Hong , Fu Henry , Yan Chun Hoi , Chiu Kwong Yuen 
Published: March 2022

AbstractBackgroundArtificial intelligence is an emerging technology with rapid growth and increasing applications in orthopaedics. This study aimed to summarize the existing evidence and recent developments of artificial intelligence in diagnosing knee osteoarthritis and predicting outcomes of total knee arthroplasty.MethodsPubMed and EMBASE databases were searched for articles published in peer-reviewed journals between January 1, 2010 and May 31, 2021. The terms included: ‘artificial intelligence’, ‘machine learning’, ‘knee’, ‘osteoarthritis’, and ‘arthroplasty’. We selected studies focusing on the use of AI in diagnosis of knee osteoarthritis, prediction of the need for total knee arthroplasty, and prediction of outcomes of total knee arthroplasty. Non-English language articles and articles with no English translation were excluded. A reviewer screened the articles for the relevance to the research questions and strength of evidence.ResultsMachine learning models demonstrated promising results for automatic grading of knee radiographs and predicting the need for total knee arthroplasty. The artificial intelligence algorithms could predict postoperative outcomes regarding patient-reported outcome measures, patient satisfaction and short-term complications. Important weaknesses of current artificial intelligence algorithms included the lack of external validation, the limitations of inherent biases in clinical data, the requirement of large datasets in training, and significant research gaps in the literature.ConclusionsArtificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. Further research to overcome the weaknesses of machine learning models may enhance reliability and allow for future use in routine healthcare settings.
A novel heterozygous TPM2 gene mutation (c.456G>C; p.Lys152Asn) in an Iranian family affected by distal arthrogryposis type 1: a case report
Authors: Neissi Mostafa , Sheikh-Hosseini Motahareh , Mohammadi-Asl Javad , Al-Badran Adnan Issa 
Published: March 2022

AbstractBackgroundDistal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders characterized by congenital contractures of the distal limb joints without a neuromuscular disease. This case study seeks to report an affected son from an Iranian family with a diagnosis of DA1 with a rare causative genetic defect.Case presentationHerein, we aimed to figure out the underlying genetic of the subject from an Iranian family with DA1. Whole-exome sequencing (WES) of all known DA1 genes was carried out in the proband of the family. WES identified a novel missense mutation, c.456G>C; p.Lys152Asn, within theTPM2gene, causing a change in one amino acid (Lysine converted to Asparagine). Moreover, this detected variant was confirmed by Sanger sequencing.ConclusionOur data expand the mutational spectra ofTPM2gene associated DA1 which is vital for screening and genetic diagnosis of the disease. Also, this detected mutation has not yet been described in patients with the DA1 phenotype.
Detection of an FYCO1 nonsense mutation in an affected patient with autosomal recessive cataract (CTRCT18): a case report
Authors: Al-Badran Raed Abdulelah , Al-Badran Adnan Issa , Mabudi Hadideh , Neissi Mostafa , Mohammadi-Asl Javad 
Published: March 2022

Abstract
Background
Autosomal recessive cataract (CTRCT18) is a rare type of congenital cataract that develops to complete and lifelong childhood blindness. This inherited disorder is one of the major visual health concerns in infants. Genetic studies discovered that various gene mutations resulted in congenital cataracts. This study reports an 8-month-old affected boy from a consanguineous family with a diagnosis of congenital cataract and a causative genetic abnormality.

Case presentation
In this study, we applied whole-exome sequencing (WES) followed by Sanger sequencing to identify probable gene defects in an affected patient with a congenital cataract. We found a homozygous disease-causing FYCO1 gene mutation (c.1387 G > T; p.G463X), located in exon 8 (NM_024513), causing a nonsense mutation that has been resulted in the stop codon. Parents are heterozygous for the detected mutation.

Conclusions
Our findings establish that this detected FYCO1 gene mutation is a pathogenic variant causing autosomal recessive cataract.
The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma
Authors: Ji Chenxing , Xu Wen , Ding Hong , Chen Zhengyuan , Shi Chengzhang , Han Jie , Yu Liang , Qiao Nidan , Zhang Yichao , Cao Xiaoyun , Zhou Xiang , Cheng Haixia , Feng Huijin , Luo Cheng , Li Zhiyu , Zhou Bing , Ye Zhao , Zhao Yao 
Published: March 2022

AbstractContextGrowth hormone pituitary adenoma (GHPA), a major subtype of pituitary adenoma (PA), can lead to progressive somatic disfigurement, multiple complications, and even increased mortality. The efficacy of current treatments is limited; thus, a novel pharmacological treatment is urgently needed. As a histone acetyltransferase (HAT) coactivator, p300 can regulate the transcription of several genes that are crucial for PA tumorigenesis and progression. However, the role of p300 and its catalytic inhibitor in GHPA is still unclear.ObjectiveWe aimed to identify the expression of p300 in GHPA and in normal pituitary glands.MethodsThe expression of p300 was detected in GHPA and normal pituitary tissues. Genetic knockdown was performed by siRNA. The efficacy of the p300 inhibitor A-485 in the cell cycle, proliferation, apoptosis, and hormone secretion was investigated by flow cytometry, ELISAs, Western blotting, and qRT-PCR. RNA sequencing, bioinformatic analysis, and subsequent validation experiments were performed to reveal the potential biological mechanism of A-485.ResultsHigh expression of p300 was found in GHPA tissues compared with normal pituitary tissues. Knockdown of p300 inhibited cell proliferation and clone formation. Treatment with A-485 suppressed cell growth and inhibited the secretion of GH in vitro and in vivo. Further mechanistic studies showed that A-485 could downregulate the expression or activity of several oncogenes, such as genes in the Pttg1, c-Myc, cAMP and PI3K/AKT/mTOR signaling pathways, which are crucial for PA tumorigenesis and progression.ConclusionOur findings demonstrate that inhibition of HAT p300 by its selective inhibitor A-485 is a promising therapy for GHPA.
Hearing improvement among children with cholesteatoma who underwent canal wall up and canal wall down surgical management
Authors: Ahmad Waseem , Akbar Sehrish , Hassan Shazia 
Published: March 2022

Objectives: The most frequently used surgical methods for treating cholesteatoma include canal wall up and canal wall down procedures. The objective of the study was to compare the hearing improvement among children with cholesteatoma who underwent canal wall up and canal wall down surgical management.
Methods: The cross-sectional analytical study design was used. The study was conducted at the ENT Department of Nishtar Medical University & Hospital Multan from 15th June to 15th Nov 2020. Forty six patients with cholesteatoma were enrolled in the study after taking informed consent. Inclusion and exclusion criteria were followed. The participants were categorized into two groups. Group-A was treated with canal wall-up surgery while Group-B was treated with canal wall down Mastoidectomy. A 12-month post-operative follow-up and the audiometry assessment were compared with pre-surgical values. Additionally, a COMOT-15 survey was administered to analyze self-perceived hearing functions. The Chi-square test was used for comparative analysis of the surgical outcome and hearing improvement among the two groups. P-value (p value<0.05) was considered statistically significant.
Results: Forty six patients were included in the study with 23 participants in each group. Among 46, 26 were male and 20 were female. The pre and post-operative mean Pure-tone average values were significantly different in (Group-A) who underwent canal wall up Mastoidectomy (p<0.05) than in Group-B, who underwent canal wall down Mastoidectomy. Similarly, hearing sub-section responses of the COMOT-15 survey favored the Canal wall technique. However, the survey showed no significant differences in the mental health status of the two groups (p<0.05).
Conclusion: Our data collected after a one-year follow-up of patients suggests canal wall up as a preferred technique for hearing improvement than canal wall down technique.
doi: https://doi.org/10.12669/pjms.38.4.4933
How to cite this:Ahmad W, Akbar S, Hassan S. Hearing improvement among children with cholesteatoma who underwent canal wall up and canal wall down surgical management. Pak J Med Sci. 2022;38(4):---------. doi: https://doi.org/10.12669/pjms.38.4.4933
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.