bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor necrosis factor alpha neutralization attenuates immune checkpoint inhibitor-induced activation of intermediate monocytes in synovial fluid mononuclear cells from patients with inflammatory arthritis
Authors: Sørensen Anne Sofie , Andersen Morten Nørgaard , Juul-Madsen Kristian , Broksø Amalie Dyrelund , Skejø Cæcilie , Schmidt Henrik , Vorup-Jensen Thomas , Kragstrup Tue Wenzel
Published: February 2022

Objective

During treatment with immune checkpoint inhibitors (ICI) such as the anti-PD-1 antibody pembrolizumab, half of patients with pre-existing inflammatory arthritis experience disease flares. The underlying immunological mechanisms have not been characterized. Here, we investigate the effect of pembrolizumab on cells involved in inflammation and destruction in the synovial joint and how immunosuppressive treatments affect the pembrolizumab-induced immune reactions.

Methods

We included synovial fluid mononuclear cells (SFMCs, n = 28) and peripheral blood mononuclear cells (PBMCs, n = 6) from patients with rheumatoid arthritis and peripheral spondyloarthritis and PBMCs from healthy controls (n = 6). Fibroblast-like synovial cells (FLSs) were grown from SFMCs. The in vitro effect of pembrolizumab was tested in SFMCs cultured for 48 h, FLS-PBMC co-cultures and in SFMCs cultured for 21 days (inflammatory osteoclastogenesis). Cells and supernatants were analyzed by ELISA, flow cytometry, and pro-inflammatory multiplex assay. Finally, the effect of the disease-modifying anti-rheumatic drugs (DMARDs) adalimumab (TNFα inhibitor), tocilizumab (IL-6R inhibitor), tofacitinib (JAK1/JAK3 inhibitor), and baricitinib (JAK1/JAK2 inhibitor) on pembrolizumab-induced immune reactions was tested.

Results

Pembrolizumab significantly increased monocyte chemoattractant protein-1 (MCP-1) production by arthritis SFMCs (P = 0.0031) but not by PBMCs from patients or healthy controls (P = 0.77 and P = 0.43). Pembrolizumab did not alter MMP-3 production in FLS-PBMC co-cultures (P = 0.76) or TRAP secretion in the inflammatory osteoclastogenesis model (P = 0.28). In SFMCs, pembrolizumab further increased the production of TNFα (P = 0.0110), IFNγ (P = 0.0125), IL-12p70 (P = 0.0014), IL-10 (P = 0.0100), IL-13 (P = 0.0044), IL-2 (P = 0.0066), and IL-4 (P = 0.0008) but did not change the production of IL-6 (P = 0.1938) and IL-1 (P = 0.1022). The SFMCs treated with pembrolizumab showed an increased frequency of intermediate monocytes (P = 0.044), and the MCP-1 production increased only within the intermediate monocyte subset (P = 0.028). Lastly, adalimumab, baricitinib, and tofacitinib treatment were able to attenuate the pembrolizumab-induced MCP-1 production (P = 0.0004, P = 0.033, and P = 0.025, respectively), while this was not seen with tocilizumab treatment (P = 0.75).

Conclusion

Pembrolizumab specifically activated intermediate monocytes and induced the production of several cytokines including TNFα but not IL-6. These findings indicate that flares in patients with pre-existing inflammatory arthritis involve monocyte activation and could be managed with TNFα neutralization.
Long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma: a case report
Authors: Ishikawa Yojiro , Suzuki Motohisa , Yamaguchi Hisashi , Seto Ichiro , Machida Masanori , Takagawa Yoshiaki , Jingu Keiichi , Kikuchi Yasuyuki , Murakami Masao
Published: February 2022

Background

Radical esophagectomy for esophageal squamous cell carcinoma has improved survival, but the rate of recurrence is high. Patients of recurrent esophageal squamous cell carcinoma after failure of chemotherapy have a poor prognosis. We herein report the achievement of long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma after failure of chemotherapy.

Case presentation

A 60-year-old Japanese man was diagnosed as having squamous cell carcinoma of the lower thoracic esophagus (cT2N0M0, stage IIA). He underwent two courses of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, and esophagectomy with three-field lymphadenectomy was performed. Microscopic findings after resection showed two lymph node metastases (ypT2N1M0, stage IIB). Five months after resection, a computed tomography scan revealed a solitary liver metastasis in the S4 area. He underwent three courses of chemotherapy with cisplatin and 5-fluorouracil; however, positron emission tomography revealed two lymph node metastases. Surgeons recommended second-line chemotherapy, but the patient refused chemotherapy and requested proton beam therapy. We performed proton beam therapy without chemotherapy for the liver metastasis and lymph node metastases, with total doses of 79.2 and 60 Gy relative biological effectiveness, respectively, according to the tumor location. An acute side effect of grade 1 dermatitis occurred after proton beam therapy, but there was no acute or late complication of more than grade 2. The patient remains in complete remission 5 years after treatment without surgery or chemotherapy.

Discussion and conclusions

Proton beam therapy exerted a curative effect on oligorecurrent esophageal squamous cell carcinoma. This is the first report on the achievement of long-term survival after definitive proton beam therapy for oligorecurrent esophageal squamous cell carcinoma.
Pathobiology of highly pathogenic H5 avian influenza viruses in naturally infected Galliformes and Anseriformes in France during winter 2015–2016
Authors: Gaide Nicolas , Lucas Marie-Noëlle , Delpont Mattias , Croville Guillaume , Bouwman Kim M. , Papanikolaou Andreas , van der Woude Roosmarijn , Gagarinov Iwan A. , Boons Geert-Jan , De Vries Robert P. , Volmer Romain , Teillaud Angélique , Vergne Timothée , Bleuart Céline , Le Loc’h Guillaume , Delverdier Maxence , Guérin Jean-Luc
Published: February 2022

In late 2015, an epizootic of Highly Pathogenic Avian Influenza (H5Nx) was registered in Southwestern France, including more than 70 outbreaks in commercial poultry flocks. Phylogenetic analyses suggested local emergence of H5 viruses which differed from A/goose/Guangdong/1/1996 clade 2.3.4.4b lineage and shared a unique polybasic cleavage site in their hemagglutinin protein. The present work provides an overview of the pathobiological picture associated with this epizootic in naturally infected chickens, guinea fowls and ducks. Upon necropsy examination, selected tissues were sampled for histopathology, immunohistochemistry and quantitative Real Time Polymerase Chain Reaction. In Galliformes, HPAIVs infection manifested as severe acute systemic vasculitis and parenchymal necrosis and was associated with endothelial expression of viral antigen. In ducks, lesions were mild and infrequent, with sparse antigenic detection in respiratory and digestive mucosae and leukocytes. Tissue quantifications of viral antigen and RNA were higher in chickens and guinea fowls compared to duck. Subsequently, recombinant HA (rHA) was generated from a H5 HPAIV isolated from an infected duck to investigate its glycan-binding affinity for avian mucosae. Glycan-binding analysis revealed strong affinity of rHA for 3’Sialyl-LacNAc and low affinity for Sialyl-LewisX, consistent with a duck-adapted virus similar to A/Duck/Mongolia/54/2001 (H5N2). K222R and S227R mutations on rHA sequence shifted affinity towards Sialyl-LewisX and led to an increased affinity for chicken mucosa, confirming the involvement of these two mutations in the glycan-binding specificity of the HA. Interestingly, the rHA glycan binding pattern of guinea fowl appeared intermediate between duck and chicken. The present study presents a unique pathobiological description of the H5 HPAIVs outbreaks that occurred in 2015–2016 in Southwestern France.
DIPPAS: a deep image prior PRNU anonymization scheme
Authors: Picetti Francesco , Mandelli Sara , Bestagini Paolo , Lipari Vincenzo , Tubaro Stefano
Published: February 2022

Source device identification is an important topic in image forensics since it allows to trace back the origin of an image. Its forensics counterpart is source device anonymization, that is, to mask any trace on the image that can be useful for identifying the source device. A typical trace exploited for source device identification is the photo response non-uniformity (PRNU), a noise pattern left by the device on the acquired images. In this paper, we devise a methodology for suppressing such a trace from natural images without a significant impact on image quality. Expressly, we turn PRNU anonymization into the combination of a global optimization problem in a deep image prior (DIP) framework followed by local post-processing operations. In a nutshell, a convolutional neural network (CNN) acts as a generator and iteratively returns several images with attenuated PRNU traces. By exploiting straightforward local post-processing and assembly on these images, we produce a final image that is anonymized with respect to the source PRNU, still maintaining high visual quality. With respect to widely adopted deep learning paradigms, the used CNN is not trained on a set of input-target pairs of images. Instead, it is optimized to reconstruct output images from the original image under analysis itself. This makes the approach particularly suitable in scenarios where large heterogeneous databases are analyzed. Moreover, it prevents any problem due to the lack of generalization. Through numerical examples on publicly available datasets, we prove our methodology to be effective compared to state-of-the-art techniques.
circPTPN4 regulates myogenesis via the miR-499-3p/NAMPT axis
Authors: Cai Bolin , Ma Manting , Zhou Zhen , Kong Shaofen , Zhang Jing , Zhang Xiquan , Nie Qinghua
Published: February 2022

Background

Circular RNAs (circRNAs) are a novel class of endogenous ncRNA, which widely exist in the transcriptomes of different species and tissues. Recent studies indicate important roles for circRNAs in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of circRNAs in myogenesis is still poorly understood. In this study, we attempted to systematically identify the circRNAs involved in myogenesis and analyze the biological functions of circRNAs in chicken skeletal muscle development.

Results

In total, 532 circRNAs were identified as being differentially expressed between pectoralis major (PEM) and soleus (SOL) in 7-week-old Xinghua chicken. Among them, a novel circRNA (novel_circ_002621), generated by PTPN4 gene, was named circPTPN4 and identified. circPTPN4 is highly expressed in skeletal muscle, and its expression level is upregulated during myoblast differentiation. circPTPN4 facilitates the proliferation and differentiation of myoblast. Moreover, circPTPN4 suppresses mitochondria biogenesis and activates fast-twitch muscle phenotype. Mechanistically, circPTPN4 can function as a ceRNA to regulate NAMPT expression by sponging miR-499-3p, thus participating in AMPK signaling.

Conclusions

circPTPN4 functions as a ceRNA to regulate NAMPT expression by sponging miR-499-3p, thus promoting the proliferation and differentiation of myoblast, as well as activating fast-twitch muscle phenotype.
Triatoma williami in intradomiciliary environments of urban areas in Mato Grosso State, Brazil: domiciliation process of a wild species?
Authors: Martins Mirian Francisca , de Moraes Sinara Cristina , Oliveira Jader , dos Santos Janaina Cipriana , Santos-Silva Ludier Kesser , Galvão Cleber
Published: February 2022

Background

Triatomines in Latin America are natural Chagas disease (ChD) vectors. Triatomine domiciliation is one of the main factors increasing the occurrence risk of this disease in humans. There are 66 triatomine species in Brazil, with three genera of significant epidemiological importance—Panstrongylus, Rhodnius, and Triatoma. Among the Triatoma species, Triatoma williami, a wild species, has been reported in Goiás, Mato Grosso, and Mato Grosso do Sul. In the Barra do Garças, Mato Grosso, the invasion by triatomines has been reported, with T. williami being the most common species. This study aimed to survey triatomine fauna and determine the Trypanosoma cruzi natural infection rates in triatomines in the urban area of Barra do Garças, Mato Grosso, Brazil.

Methods

Triatomine specimens were sampled by passive surveillance or active search by agents combating endemic diseases from 2019 to 2020. A parasitological feces diagnosis was performed to detect the presence of T. cruzi after the specimens were identified. Concerning T. cruzi identification, molecular diagnosis and genetic sequencing were performed to determine the strain, also called discrete typing units (DTUs).

Results

The 211 triatomines were collected, distributed in specimens of T. williami (84.4%), P. geniculatus (3.3%), P. diasi (1.4%), and R. neglectus (10.9%). Two colonies of T. williami were found through morphological analyses. These insects were sampled inside domiciles in an urban area neighboring Jardim Pitaluga (15° 51′57.7″ N, 052° 16′ 04.5 E). The records were sampled in September 2019 and January 2021. The rate of natural infection by T. cruzi was 39.4%. Two T. williami specimens from the sampled colonies were positive for the T. cruzi strain DTU IV.

Conclusions

This is the first time that T. williami has been confirmed in an urban area of Barra do Garças, Mato Grosso, Brazil. Further studies are needed for a clearer understanding of the ecology of this species for prevention and control mechanisms since its sampled specimens had a high rate of natural infection by T. cruzi.

Graphical Abstract
Social exclusion, thwarted belongingness, and perceived burdensomeness: construct validity and psychometric properties of the Interpersonal Needs Questionnaire among patients with sexually transmitted infections in Shanghai, China
Authors: Gong Ruijie , Wang Suping , Ji Yucheng , Li Zhile , Chang Ruijie , Zhang Shuxian , Yu Xiaoyue , Xu Chen , Cai Yong , Ni Yang
Published: February 2022

Background

Sexually transmitted infections (STIs) are a serious public health problem worldwide. Patients with STIs have a high rate of psychosocial problems and may perceive unmet interpersonal needs, which is considered a proximal and sufficient cause of suicidal thoughts and behaviors. The present study examined the construct validity and psychometric properties of the 15-item Interpersonal Needs Questionnaire among patients with STIs in Shanghai, China.

Methods

We recruited 910 patients with STIs (438 males and 472 females; mean age = 38.72, standard deviation [SD] = 13.034) from the Shanghai Skin Disease Hospital using accidental sampling. Baseline descriptive statistics were calculated using R 4.0.0, and a latent variable model was developed using Mplus 7.4.

Results

The construct validity results supported a latent variable measurement model with three distinct but related constructs (thwarted belongingness, perceived burdensomeness, and social exclusion) (p < 0.001, χ2/df = 2.475, root mean square error of approximation = 0.057, comparative fit index = 0.931, Tucker–Lewis index = 0.916, standardized root mean residual = 0.044). The Cronbach’s α and McDonald’s ω values were 0.849 and 0.767 for the total scale, 0.888 and 0.889 for perceived burdensomeness, 0.764 and 0.777 for social exclusion, and 0.892 and 0.893 for thwarted belongingness. Interpersonal needs were significantly associated with low self-esteem (r = 0.539), loneliness (r = 0.573), depression (r = 0.338), entrapment (r = 0.420), defeat (r = 0.579), and low perceived social support (r = 0.424).

Conclusions

This was the first study to highlight social exclusion as a distinct but related dimension of interpersonal needs. This finding indicates that patients with STIs perceive high social exclusion. Therefore, health providers should consider the psychological status of these patients and implement strategies to support their integration into society.
Comparison of Ex-PRESS implantation versus trabeculectomy combined with phacoemulsification in primary open-angle glaucoma: a retrospective in vivo confocal microscopy study
Authors: Zhang Yuqiao , He Beiting , Zhang Yulin , Zeng Jin , Chen Yanlei , Niu Yongyi , Yu Honghua , Qin Yongjie , Zhang Hongyang
Published: February 2022

Background

To compare the efficacy of Ex-PRESS implantation versus trabeculectomy combined with phacoemulsification.

Methods

A retrospective 12-month study on patients with coincident primary open-angle glaucoma (POAG) and cataract. The patients underwent combined phacoemulsification and Ex-PRESS implant (Phaco-ExPRESS, n = 35) or phacotrabeculectomy (Phaco-Trab, n = 35). The morphological structures of the filtering bleb were examined by slit-lamp, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Complete success was defined as postoperative intraocular pressure (IOP) < 18 mmHg without the use of anti-glaucoma medication. Qualified success was defined as postoperative IOP < 18 mmHg with or without anti-glaucoma medications. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, and 12 months.

Results

No significant difference in the variables such as age, IOP and perimetry was found between the groups of Phaco-ExPRESS and Phaco-Trab. At the one-year postoperative visit for filtering blebs, Phaco-ExPRESS increased the mean area of epithelial microcysts significantly from 0.10 ± 0.05 to 0.20 ± 0.09 μm2 per μm2, while Phaco-Trab decreased the mean area significantly from 0.08 ± 0.04 to 0.04 ± 0.06 μm2 per μm2. Notably, the hyperreflective dots detected by IVCM decreased by 84.9% in Phaco-ExPRESS but increased by 36.3% in Phaco-Trab. The hyperreflective dots were further identified as neutrophil- and monocyte-like cells. The number of these cells were negatively correlated with the microcysts area (r =  − 0.7, P < 0.01) but positively associated with the grade of connective tissue (r = 0.5, P < 0.01). By creating different microstructural changes in the filtering blebs, Phaco-ExPRESS produced a higher complete success rate (84.9% vs. 41.2%, P < 0.01) and significant decrease in the number of anti-glaucoma medications (P < 0.01) when compared with those in Phaco-Trab. However, the qualified success showed no significant difference between the two groups (100.0% vs. 91.2%, P = 0.24).

Conclusions

At the one-year follow-up, Phaco-ExPRESS generated better filtering bleb with larger area of microcysts, looser connective tissues, and less inflammation than that of Phaco-Trab, providing adequate IOP control and less IOP-lowering medications. These findings indicate that Phaco-ExPRESS could be more preferred than Phaco-Trab for the treatment of patients with coincident POAG and cataract.
Machine and cognitive intelligence for human health: systematic review
Authors: Chen Xieling , Cheng Gary , Wang Fu Lee , Tao Xiaohui , Xie Haoran , Xu Lingling
Published: February 2022

Brain informatics is a novel interdisciplinary area that focuses on scientifically studying the mechanisms of human brain information processing by integrating experimental cognitive neuroscience with advanced Web intelligence-centered information technologies. Web intelligence, which aims to understand the computational, cognitive, physical, and social foundations of the future Web, has attracted increasing attention to facilitate the study of brain informatics to promote human health. A large number of articles created in the recent few years are proof of the investment in Web intelligence-assisted human health. This study systematically reviews academic studies regarding article trends, top journals, subjects, countries/regions, and institutions, study design, artificial intelligence technologies, clinical tasks, and performance evaluation. Results indicate that literature is especially welcomed in subjects such as medical informatics and health care sciences and service. There are several promising topics, for example, random forests, support vector machines, and conventional neural networks for disease detection and diagnosis, semantic Web, ontology mining, and topic modeling for clinical or biomedical text mining, artificial neural networks and logistic regression for prediction, and convolutional neural networks and support vector machines for monitoring and classification. Additionally, future research should focus on algorithm innovations, additional information use, functionality improvement, model and system generalization, scalability, evaluation, and automation, data acquirement and quality improvement, and allowing interaction. The findings of this study help better understand what and how Web intelligence can be applied to promote healthcare procedures and clinical outcomes. This provides important insights into the effective use of Web intelligence to support informatics-enabled brain studies.
Simulating employment and fiscal effects of public investment in high-quality universal childcare in the UK
Authors: De Henau Jerome
Published: February 2022

This paper simulates the likely fiscal and employment effects of a vast public annual investment programme of free universal high-quality early childhood education and care (ECEC) services in the UK. It examines the extent to which it would pay for itself fiscally for different scenarios of pay increases. Investing in high-quality universal ECEC benefits all children by improving their life chances, especially for those living in lower income families. It also generates larger employment effects than other more typical investment policies such as construction projects and fosters gender equality in employment: not only it provides many high-quality jobs for women, it also allows many mothers to improve their lifetime earnings prospects by freeing up their childcare constraints. This in turn has beneficial fiscal revenue effects for the government. Estimations of annual public expenditure for a system of highly qualified and well-paid childcare staff with low child-to-staff ratios are performed, with universal coverage for all pre-school children aged 6 months to 4.5 years. Labour demand and matching supply effects are also simulated using input–output methods, for different take-up rates of the programme. A microsimulation tool is used to calculate increases in household income and tax liabilities and decreases in social security benefits spending. This results in a net annual funding requirement of between 28 and 39% of the gross investment. Two funding methods are then explored: raising taxation in a progressive way and recouping the cost over time from persistent mothers’ increased earnings. The former would entail a net additional contribution by the richest 20% of households of at most 0.4% of their income; the latter would require 21 to 31 years to offset the programme on average, which is within a typical working life-course following a first child’s birth, of 35 years.
Positive end-expiratory pressure setting based on transpulmonary pressure during robot-assisted laparoscopic prostatectomy: an observational intervention study
Authors: Nakazawa Koichi , Kodaira Ami , Matsumoto Rika , Matsushita Tomoko , Yoshikawa Ryotaro , Ishida Yusuke , Uchino Hiroyuki
Published: February 2022

Background

In robot-assisted laparoscopic prostatectomy (RALP), concerns include the formation of atelectasis and reduced functional residual capacity. The present study aimed to examine the feasibility of positive end-expiratory pressure (PEEP) setting based on transpulmonary pressure (Ptp) as well as the effects of incremental PEEP on respiratory mechanics, blood gases, cerebral oxygenation (rSO2), and hemodynamics.

Methods

Fourteen male patients who were scheduled to receive RALP were recruited. Patients received mechanical ventilation (tidal volume of 6 mL kg−1) and were placed in Trendelenburg position with positive-pressure capnoperitoneum. PEEP levels were increased from 0 to 15 cmH2O (5 cmH2O per increase) every 30 min. PEEP levels were assessed where end-expiratory Ptp levels of ≥0 cmH2O were achieved (PtpEEP0). Airway pressure, esophageal pressure, cardiac index, and blood gas and rSO2 values were measured after 30 min at each PEEP step and respiratory mechanics were calculated.

Results

With increasing PEEP levels from 0 to 15 cmH2O or PtpEEP0, the values of PaO2 and respiratory system compliance increased, and the values of driving pressure decreased. The median PEEP level associated with PtpEEP0 was 15 cmH2O. Respiratory system compliance values were higher at PtpEEP0 than those at PEEP5 (P = 0.02). Driving pressure was significantly lower at PtpEEP0 than at PEEP5 (P = 0.0036). The cardiac index remained unchanged, and the values of rSO2 were higher at PtpEEP0 than at PEEP0 (right; P = 0.0019, left; P = 0.036).

Conclusions

PEEP setting determined by transpulmonary pressure can help achieve higher respiratory system compliance values and lower driving pressure without disturbing hemodynamic parameters.
Efficiency of femoral nerve block for recovery after primary total knee arthroplasty
Authors: Tekgül Zeki Tuncel , Bilgin Mehmet Uğur , Kayalı Cemil
Published: February 2022

Background

Femoral nerve block (FNB) is a suitable option for pain management and recovery after total knee arthroplasty (TKA). It is usually used along with a multimodal analgesia protocol. The major disadvantage of FNB is the risk of quadriceps muscle strength loss. This study aims to compare the efficiency of the FNB with two different concentrations of bupivacaine for recovery after TKA. We primarily aim to provide adequate analgesia with a lower concentration of bupivacaine (0.125%) rather than the usual concentration (0.25%). Secondarily, we aim to compare the degree of motor block, opioid consumption, and ambulation time between the groups. The study was conducted as randomized, controlled, and double-blind. Sixty three patients were randomized into three groups: G125 (n:21) received FNB with 20ml of 0,125% bupivacaine, G25 (n:21) received 10ml of 0,25% bupivacaine and GCont (n:21) received no block.

Results

For GCont, pain scores were significantly higher at 2nd, 6th, 12th, and 24th hours postoperatively, total opioid consumption was higher (G125: 75 mg, G25: 0 mg, GCont: 280 mg,p< 0.001) and first opioid demand time was earlier (G125: 12th hour, G25:21st hour GCont:2nd hour,p: 0.002). First knee flexion time and ambulation time were also delayed for GCont. G25 had lower scores for quadriceps muscle strength (manual test at 6th hour, G25: 3/5, G125: 4/5, GCont:5/5,p< 0.001) compared to other groups.

Conclusions

G125 had lower quadriceps muscle strength loss compared to the G25; earlier ambulation and flexion times, low opioid consumption, and low pain scores compared to the control group. In this respect, we believe the femoral nerve block with 0.125% bupivacaine proves to be a suitable option for analgesia with the potential of maintaining enough muscle strength for recovery after TKA.

Trial registration

ClinicalTrials.govProtocol Registration and Results System, NCT03623230. Registered 09 August 2018, athttps://clinicaltrials.gov/ct2/show/NCT03623230
Regulation of stem cell identity by miR-200a during spinal cord regeneration
Authors: Walker Sarah E. , Sabin Keith Z. , Gearhart Micah D. , Yamamoto Kenta , Echeverri Karen
Published: February 2022

Axolotls are an important model organism for multiple types of regeneration, including functional spinal cord regeneration. Remarkably, axolotls can repair their spinal cord after a small lesion injury and can also regenerate their entire tail following amputation. Several classical signaling pathways that are used during development are reactivated during regeneration, but how this is regulated remains a mystery. We have previously identified miR-200a as a key factor that promotes successful spinal cord regeneration. Here, using RNA-seq analysis, we discovered that the inhibition of miR-200a results in an upregulation of the classical mesodermal marker brachyury in spinal cord cells after injury. However, these cells still express the neural stem cell marker sox2. In vivo cell tracking allowed us to determine that these cells can give rise to cells of both the neural and mesoderm lineage. Additionally, we found that miR-200a can directly regulate brachyury via a seed sequence in the 3′UTR of the gene. Our data indicate that miR-200a represses mesodermal cell fate after a small lesion injury in the spinal cord when only glial cells and neurons need to be replaced.
Fiddler crab electroretinograms reveal vast circadian shifts in visual sensitivity and temporal summation in dim light
Authors: Brodrick Emelie A. , How Martin J. , Hemmi Jan M.
Published: February 2022

Many animals with compound eyes undergo major optical changes to adjust visual sensitivity from day to night, often under control of a circadian clock. In fiddler crabs, this presents most conspicuously in the huge volume increase of photopigment-packed rhabdoms and the widening of crystalline cone apertures at night. These changes are hypothesised to adjust the light flux to the photoreceptors and to alter optical sensitivity as the eye moves between light- and dark-adapted states. Here, we compared optical sensitivity in fiddler crab (Gelasimus dampieri) eyes during daytime and night via three electroretinogram (ERG) experiments performed on light- and dark-adapted crabs. (1) Light intensity required to elicit a threshold ERG response varied over six orders of magnitude, allowing more sensitive vision for discriminating small contrasts in dim light after dusk. During daytime, the eyes remained relatively insensitive, which would allow effective vision on bright mudflats, even after prolonged dark adaptation. (2) Flicker fusion frequency (FFF) experiments indicated that temporal summation is employed in dim light to increase light-gathering integration times and enhance visual sensitivity during both night and day. (3) ERG responses to flickering lights during 60 min of dark adaptation increased at a faster rate and to a greater extent after sunset compared with daytime. However, even brief, dim and intermittent light exposure strongly disrupted dark-adaptation processes. Together, these findings demonstrate effective light adaptation to optimise vision over the large range of light intensities that these animals experience.
Chalcogen Bond versus Halogen Bond: Changing Contributions in Determining the Crystal Packing of Dihalobenzochalcogenadiazoles
Authors: Ishigaki Yusuke , Shimomura Kai , Asai Kota , Shimajiri Takuya , Akutagawa Tomoyuki , Fukushima Takanori , Suzuki Takanori
Published: February 2022

In the crystals of 4,7-dihalobenzo[c][1,2,5]chalcogenadiazoles, the molecules are connected by two competing secondary bonding interactions: chalcogen bond (ChB) and halogen bond (HaB). Because the strengths of ChB and HaB change according to the kind of chalcogen (E: S, Se, Te) and halogen (X: Cl, Br, I), their relative contributions in determining the crystal packing can also change. Six newly determined crystal structures as well as 3 previously reported structures can be categorized into two groups: ChB-dominant and HaB-dominant structures. HaB in which X = I is strong enough to dictate the crystal packing of compounds with E = S and Se, but not where E = Te, whereas HaB in which X = Cl or Br has little effect on ChB-dominant molecular networks in crystals. The observed changing contributions of ChB and HaB may be useful for designing new supramolecular synthons for crystal engineering.
Performance and preference of problem-based learning (PBL) and lecture-based classes among medical students of Nepal
Authors: Adhikari Yadav Saroj , Poudel Sangeeta , Pandey Oshna , Jaiswal Dhiraj Prasad , Malla Bhupendra Prakash , Thakur Brajesh Kumar , Gautam Swotantra , Pandey Sirish Raj
Published: February 2022

Background: PBL (problem based learning) is new active learning educational strategy that has been extensively tested and used in recent years. This study aims to compare students' understanding and knowledge retention when taught through PBL and lecture-based classes and compare PAHS students' perceptions of PBL and lectures in medical education.

Methods: This is a cross-sectional study of medical students of a PBL based medical school in Nepal, a non-Western low-income country. Ethical approval was given by the institutional research committee of the Patan Academy of Health Sciences. Understanding and knowledge retention was assessed with 50 vignette-based multiple-choice questions, half of which were taught through PBL sessions, and the remaining half were taught in didactic lectures during basic science years of medical school. A separate pre-validated perception questionnaire was used to assess students' preferences regarding PBL and lectures.

Results: Out of 107 students, 99 participated in the understanding and knowledge retention questionnaires and 107 completed perception questionnaires. Understanding and knowledge retention of students was found to be the same for topics taught by PBL and lectures, with median scores of 17 and s16, respectively. PBL were mostly preferred for the physiology (59.81%), pathology (51.40%) and pharmacology (53.27%) concepts, and lectures were mostly preferred for the anatomy (78.50%), biochemistry (45.79%), and microbiology (42.99%) topics. Students wanted the same concepts to be taught through both PBL and lectures, especially for anatomy.

Conclusions: Understanding and knowledge retention is the same for topics taught by either PBL or lectures during the basic science years of undergraduate medical education. Students prefer PBL for physiology, pathology, and pharmacology-related concepts, conventional didactic lecture for physiology and microbiology, and a combination of lecture and PBL sessions for anatomy.
Students’ perception of online learning amidst the Covid-19 pandemic: A study of junior, senior high school and college students in a remote area
Authors: Harefa Senida , Sihombing Grace Lamudur Arta
Published: February 2022

Background: The COVID-19 pandemic has brought about many changes in all sectors of life, especially in the field of education. These changes aim to make the learning process more effective in the pandemic environment. However, it can be challenging, as some students do not give positive responses to these changes, especially those in remote areas. This article aims to identify and report students' perceptions about the effectiveness of online learning during the COVID-19 pandemic in the remote North Tapanuli region of Indonesia.

Methods: In this study, data were obtained using an online survey involving 30 students from three levels of education, namely junior high school, senior high school, and college. They are students who the teacher appoints as class administrators; through them, the teacher communicates about everything—learning activities. So compared to his other friends, they know more about the implementation of online learning during the covid 19 pandemic. In addition, schools in remote areas have fewer students than schools in big cities. So we conclude that this research is considered representative with thirty students as the sample. The data gathered from the survey were analyzed using quantitative descriptive methods.

Results: Results show that online learning is considered less effective by students in remote areas; this happens because communication networks and infrastructure do not adequately support them to follow online learning.

Conclusion: Teachers need to evaluate how to teach as well as re-design models and approaches to be applied in learning. This can be achieved by adjusting to the student’s current situation to generate interest and willingness to learn online.
Data analytics competency and religiosity influence on external auditors’ performance in Malaysia
Authors: Jaffar Nahariah , Bin Ahmad Abdul Aziz , Sulaiman Noor Adwa
Published: February 2022

Background - Data analytics can support the external auditors’ judgements. However, little is known about the external auditors’ data analytics competency. Likewise, role of religiosity in enhancing the external auditors’ performance is also inadequately investigated. This study examined: 1) the effects of data analytics competency on the external auditors’ performance, and 2) the moderating effects of religiosity on data analytics competency and external auditors’ performance relationship.

Methods – Survey was conducted on 201 external auditors. Data analytics competency dimensions, namely, personal capabilities, professional expertise, technical skills, technologies and tools expertise were examined. Religiosity was measured by level and dimension (faith, virtue and optional).

Results – Data analytics competency (personal capabilities) has a significant positive effect on the Muslim external auditors’ performance, whereas data analytics competency (technologies and tools expertise) has a significant positive affect on the non-Muslim external auditors’ performance. Level of religiosity has significant moderating effect on the relationship between data analytics competency (technologies and tools expertise) and Muslim external auditors’ performance. Nonetheless, level of religiosity does not moderate the relationship between data analytics competency and the performance of non-Muslim external auditors. Religiosity (virtue) has significant moderating effect on the relationship between data analytics competency (personal capabilities) and Muslim external auditors’ performance. Meanwhile, religiosity (faith) has a significant moderating effect on the relationship between data analytics competency (technologies and tools expertise) and non-Muslim external auditors’ performance.

Conclusion – This study demonstrates that data analytics competency and religiosity can influence the external auditors’ performance.
Colorectal cancer on a dish: exploring the 3D-sphere culture of primary colorectal cancer cells from an Indonesian perspective
Authors: Abdullah Murdani , Noor DR , Utari Amanda Pitarini , Muzellina Virly Nanda , Rahadiani Nur , Antarianto Radiana Dhewayani
Published: February 2022

Background : Colorectal Cancer (CRC) is one of the deadliest types of cancer and has emerged as one of Indonesia's most devastating diseases. The growing number of colorectal cancer cases is frequently undiagnosed until the disease has progressed to a metastatic stage. This issue has lasted for years, limiting therapy options and resulting in a bad prognosis for the majority of patients. Thus, the purpose of this work is to develop a CRC detection method for Indonesia and other low-middle income nations that integrates in vitro 3D culture, molecular analysis, and in silico analysis.

Methods : Colorectal cancer biopsies were transported to the lab and underwent mechanical disaggregation and centrifuged at 300 x g for five minutes. Approximately 10,000 cells were seeded in each Nunc-Sphera 96-well plate (u-bottom) for the following 7 days in standard culture medium. The 3D-sphere was harvested and RNA was extracted afterwards. Molecular analysis was performed using qPCR and the Human Cancer Pathway Profiler. Protein interaction and pathway analysis were conducted using STRING and Reactome online tools.

Results :  Following initial seeding, primary CRC 3D-spheres were grown for 14–16 days. Gene profiling and in silico analyses suggest that CDC20, AURKA, and ACLY are expressed at lower levels than the positive control in the 3D-sphere. These markers have been implicated in metastasis, CRC proliferation, and as a drug target ligand.

Conclusion : A combination of 3D culture, gene profiling, and in silico analysis is feasible to detect CRC for Indonesia and other low- and middle-income countries. A future possibility is to use minicolorectal cancer in a dish for ex vivo cancer modeling and pharmacological testing.
Putting youth at the centre: co-design of a community-based intervention to improve HIV outcomes among youth in Zimbabwe
Authors: Mackworth-Young Constance , Dringus Stefanie , Dauya Ethel , Dziva Chikwari Chido , Mavodza Constancia , Tembo Mandikudza , Doyle Aoife , McHugh Grace , Simms Victoria , Wedner-Ross Maurice , Apollo Tsitsi , Mugurungi Owen , Ferrand Rashida , Bernays Sarah
Published: February 2022

Abstract

Background

Youth have disproportionately poor HIV outcomes. We aimed to co-design a community-based intervention with youth to improve HIV outcomes among 16-24 year-olds, to be trialled in Zimbabwe.

Methods

We conducted 90 in-depth interviews with youth, family members, community gatekeepers, and healthcare providers to understand the barriers to uptake of existing HIV services. The interviews informed an outline intervention, which was refined through two participatory workshops with youth, and subsequent pilot-testing.

Results

Participants considered existing services inaccessible and unappealing:  health facilities were perceived to be for ‘sick people’, centred around HIV and served by judgemental providers. Proposed features of an intervention to overcome these barriers, included: i) delivery in a youth-only community space; ii) integration of HIV services with broader health services; iii) non-judgemental skilled healthcare providers; iv) entertainment to encourage attendance; and v) tailored timings and outreach. The intervention framework stands on three core pillars, based on optimising: i) access: community-based youth-friendly settings; ii) uptake and acceptability: service branding, confidentiality, and social activities; and iii) content and quality: integrated HIV care cascade, high quality products, and trained providers.

Conclusions

Ongoing meaningful youth engagement is critical to designing HIV interventions if access, uptake, and coverage is to be achieved.
A Newsvendor Approach to Design of Surgical Preference Cards
Authors: Görgülü Berk , Sarhangian Vahid
Published: February 2022

Surgical procedures require a large number of consumable supplies that need to be kept in hospital inventory and transported to the operating rooms (OR) before the surgery. A surgical preference card (SPC) provides a list of items to be prepared for each surgery. For each item, a SPC also specifies how many should be taken to the OR (fill quantity). As the usage of most consumables in the OR is subject to uncertainty, the cards also specify how many of the filled items should be opened at the beginning of the surgery (open quantity). The fill and open quantities control the flow of consumables between the hospital inventory and the ORs and directly affect the wastage in ORs. In this work, we formulate the problem of determining the fill and open quantities on the preference cards as a stochastic optimization problem, where the objective is to minimize a weighted sum of the expected wastage and operational costs. We show that, as in the newsvendor problem, the optimal solution for the fill and open quantities takes the form of critical quantiles of the item usage distribution in the OR. The solution form together with historical usage data provide a data-driven approach to design of SPCs, as well as insights on the value of including an open decision. We demonstrate our approach using extensive numerical experiments and real usage data from a Canadian hospital. The results suggest a potential for significant reduction of wastage and operational costs in the ORs.
JEJAK KOLONIAL DAN PERAN ORIENTALISME DALAM KUMPULAN CERPEN TEH DAN PENGHIANAT KARYA IKSAKA BANU
Authors: Nalurita Baiq Annisa Yulfana , Apriyani Tristanti
Published: February 2022

The colonial period was the planting of orientalist concepts towards the East, where the differences between East and West were very much shown. This of course did not escape the views of several Indonesian writers and writers who then tried to record this phenomenon in their literary works. One of the Indonesian writers, Iksaka Banu, who discusses the conflict between the natives and the Dutch, the Dutch and ethnic Chinese, to the conflict between the Dutch and the Dutch in various experiences and one of them is Iksaka Banu's latest collection of short stories entitled Teh dan Penghianat which was just published in 2019. This research using qualitative descriptive method aims to describe the form and role of orientalism in the collection of Teh and the traitor by Iksaka Banu by taking two short stories as material for analysis, namely 'Teh dan Pengianat' and ‘Belenggu Emas’. The data collection technique was carried out by document study techniques in short stories, namely by collecting data in the form of document archives, including books and journals. Meanwhile, the data triangulation process in the form of theoretical triangulation, data source triangulation and researcher triangulation, was carried out by the author to check the validity of the data. By using the theory put forward by Edward Said, this research concludes that in the short story Teh dan Pengtangan, there can be found several depictions of the East in the context of orientalism which symbolized by indigenous and ethnic Chinese. Meanwhile, in the short story Belenggu Emas, the depiction of the east in the context of orientalism is described as an indigenous community that needs to be improved or educated
Running a weight-management programme with a psychological focus within a lymphoedema service
Authors: Lawrence Paula
Published: February 2022

Weight management and psychological health are intertwined. Patients in this context are often mindful of how to eat healthily and what they need to do to lose weight, but frequently self-sabotage, with external influences often impact any attempted weight-loss approach. Consequently, any form of lymphoedema management is also thwarted and vicious cycles between success and rebound occur. This article describes a 6-week weight-management programme that took place before the COVID-19 pandemic. The programme focused exclusively on the expectation that, if a patient's psychological health could be improved, weight reduction would occur as a result, and, in turn, any positive effects on adherence with lymphoedema treatments could be observed.
Chronic kidney disease and renal replacement therapy: an overview for the advanced clinical practitioner
Authors: Price Ian N , Wood Alison F
Published: February 2022

Chronic kidney disease (CKD), also known as chronic renal failure (CRF), is a common, globally significant condition, with associated significant mortality and morbidity. Due to the disease prevalence, advanced clinical practitioners (ACPs) in a variety of primary and secondary care settings will encounter patients with this diagnosis who will require care and treatment. This article examines definitions of CKD, describes a clinical approach to a patient with CKD, including key history and examination findings, and provides a brief overview of renal replacement strategies for the patient with end-stage renal failure. ACPs require a thorough understanding of this condition and the key elements of treatment and care in this population.
Disputes about a person's best interests: Is there a need to go to court?
Authors: Griffith Richard
Published: February 2022

Richard Griffith, Head of Health Law and Ethics, School of Health and Social Care, Swansea University, considers whether it is necessary to seek an order from the Court of Protection where there is a dispute as to what care and treatment is in the best interests of a patient lacking capacity