bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrence of cat-scratch disease and paradoxical tuberculosis-IRIS lymphadenopathy: a case report
Authors: Eleftheriotis Gerasimos , Skopelitis Elias
Published: March 2022

Background

Mycobacterial infections can cause significant morbidity when cellular immunity is compromised. Patients with AIDS can be affected directly from infection or through mycobacterial IRIS, especially if they are previously untreated for HIV. Herein a case of tuberculous lymphadenitis is reported, which primarily responded to antimicrobials but complicated by IRIS and cat-scratch disease at a later course.

Case presentation

A 23-year-old man, intravenous drug user with untreated HIV and HCV infection presented with fever and painful cervical lymphadenopathy. Mycobacterium tuberculosis was isolated from PCR and culture of ultrasound-guided lymph node aspirate and a four-drug anti-TB regimen was subsequently administered, leading to complete resolution of clinical and laboratory abnormalities. Given the patient’s CD4 count (67 cells per mm3), antiretroviral treatment started seven weeks after TB treatment initiation. Within the first month of ART fever recurred along with cervical lymph node inflammation. Paradoxical IRIS was considered as the most probable diagnosis but workup expanded, revealing acute Bartonella infection. A posteriori, the patient remembered being scratched by a stray cat two weeks before his new symptoms started. Doxycycline and corticosteroid monotherapy failed to resolve symptoms, whereas a combination of doxycycline for 3 months and methylprednisolone with long-term tapering led to negative follow-up Bartonella antibodies and complete clinical and biochemical response, without recurrence.

Conclusions

Co-infection with TB and Bartonella presenting with lymphadenitis is unusual. Cat-scratch disease can be a rare clinical presentation of Bartonella infection in patients with AIDS, but coexistence of bartonellosis and paradoxical IRIS has never been reported before. However, physicians treating people living with HIV should be aware of this potential concurrence. Early testing for Bartonella infection could be offered in patients with TB and HIV co-infection in case of acute deterioration or partial response to treatment, especially if they have a history of cat exposure, since clinical picture can be indistinguishable.
Normal pressure hydrocephalus associated with COVID-19 infection: a case report
Authors: Vasconcelos Thaís de Maria Frota , Nóbrega Paulo Ribeiro , Ferreira Glauber de Menezes , de Souza Moysés Loiola Ponte , Vanderlei Alander Sobreira , de Castro José Daniel Vieira , Braga-Neto Pedro , Sobreira-Neto Manoel Alves
Published: March 2022

Background

COVID-19 is a pandemic disease responsible for many deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) 2 months after acute COVID19 infection, in a patient without other risk factors.

Case presentation

A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms.

Conclusion

Other infections such as syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.
Herpes simplex encephalitis following ChAdOx1 nCoV-19 vaccination: a case report and review of the literature
Authors: Moslemi Mohammadreza , Ardalan Mohammadreza , Haramshahi Morteza , Mirzaei Homa , Sani Sahba Khosousi , Dastgir Ramtin , Dastgir Nima
Published: March 2022

Background

Ever since the administration of early doses of COVID-19 vaccines, instances of adverse effects have been reported. Viral infections, specifically herpes simplex reinfection and coinfections, have been reported following administration of different types of vaccines. To our knowledge, there have not been any reports of herpes simplex encephalitis following administration of any type of COVID-19 vaccine to date.

Case presentation

In this article intends to report a case of herpes simplex encephalitis in a 27-year-old male patient who was vaccinated with the ChAdOx1 nCoV-19 vaccine.

Conclusions

Our study suggests a possible but very rare side effect of ChAdOx1 nCoV-19 vaccine, which requires immediate medical attention and can lead to devastating consequences if left undiagnosed and untreated.
Differentiation between combined hepatocellular cholangiocarcinoma and hepatocellular carcinoma: comparison of diagnostic performance between ultrasomics-based model and CEUS LI-RADS v2017
Authors: Li Chao-qun , Zheng Xin , Guo Huan-ling , Cheng Mei-qing , Huang Yang , Xie Xiao-yan , Lu Ming-de , Kuang Ming , Wang Wei , Chen Li-da
Published: March 2022

Background

The imaging findings of combined hepatocellular cholangiocarcinoma (CHC) may be similar to those of hepatocellular carcinoma (HCC). CEUS LI-RADS may not perform well in distinguishing CHC from HCC. Studies have shown that radiomics has an excellent imaging analysis ability. This study aimed to establish and confirm an ultrasomics model for differentiating CHC from HCC.

Methods

Between 2004 and 2016, we retrospectively identified 53 eligible CHC patients and randomly included 106 eligible HCC patients with a ratio of HCC:CHC = 2:1, all of whom were categorized according to Contrast-Enhanced (CE) ultrasonography (US) Liver Imaging Reporting and Data System (LI-RADS) version 2017. The model based on ultrasomics features of CE US was developed in 74 HCC and 37 CHC and confirmed in 32 HCC and 16 CHC. The diagnostic performance of the LI-RADS or ultrasomics model was assessed by the area under the curve (AUC), accuracy, sensitivity and specificity.

Results

In the entire and validation cohorts, 67.0% and 81.3% of HCC cases were correctly assigned to LR-5 or LR-TIV contiguous with LR-5, and 73.6% and 87.5% of CHC cases were assigned to LR-M correctly. Up to 33.0% of HCC and 26.4% of CHC were misclassified by CE US LI-RADS. A total of 90.6% of HCC as well as 87.5% of CHC correctly diagnosed by the ultrasomics model in the validation cohort. The AUC, accuracy, sensitivity of the ultrasomics model were higher though without significant difference than those of CE US LI-RADS in the validation cohort.

Conclusion

The proposed ultrasomics model showed higher ability though the difference was not significantly different for differentiating CHC from HCC, which may be helpful in clinical diagnosis.
The effect of blister packaging Iron and Folate on adherence to medication and hemoglobin levels among pregnant women at National Referral Hospital antenatal clinics in a low to middle income country: a Randomised Controlled Trial (The IFAd Trial)
Authors: Byamugisha Josaphat , Adero Nancy , Kiwanuka Tusuubira S. , Nalwadda Christine K. , Ntuyo Peter , Namagembe Imelda , Nabunya Evelyn , Nakirijja Emily , Mwadime-Ngolo Robert , Mukasa David Christopher , Ononge Sam
Published: March 2022

Introduction

Anemia in pregnancy is an important global public health problem. It is estimated that 38% of pregnant women worldwide are anemic. In Africa, literature from observational studies show 20% of maternal deaths are attributed to anemia. In Uganda, 50% of pregnant women have iron deficiency anaemia. The proportion of pregnant women receiving Iron-Folic acid (IFA) supplementation has improved. However, the number of IFA pills consumed is still low. We carried out a randomized controlled trial to determine the effect of dispensing blister and loose packaged IFA pills on adherence measured by count on next return visit and hemoglobin levels among pregnant women at two National Referral Hospitals in Kampala, Uganda.

Methods

This trial was conducted between April and October 2016. Nine hundred fifty pregnant women at ≤28 weeks were randomized to either the blister (intervention arm) or loose (control arm) packaged IFA. The participants completed the baseline measurements and received 30 pills of IFA at enrolment to swallow one pill per day. We assessed adherence by pill count and measured hemoglobin at four and 8 weeks. The results were presented using both intention-to-treat and per-protocol analysis.

Results

There were 474 participants in the control and 478 in the intervention arms. Adherence to IFA intake was similar in the two groups at 4th week (40.6 and 39.0%,p = 0.624) and 8th week (51.9 and 46.8%,p = 0.119). The mean hemoglobin level at 4 weeks was higher in the blister than in the loose packaging arms (11.9 + 1.1 g/dl and 11.8 + 1.3 g/dl, respectively;p = 0.02), however, similar at week 8 (12.1 + 1.2 and 12.0 + 1.3, respectively;p = 0.23). However, over the 8-week period blister packaging arm had a higher change in hemoglobin level compared to loose package (blister package 0.6 ± 1.0; loose packaging 0.2 ± 1.1; difference: 0.4 g/dL (95% CI: 0.24–0.51 g/dL);p = 0.001. There were no serious adverse events.

Conclusions

Our results showed no effect of blister packaging on IFA adherence among pregnant women. However, our findings showed that blister packaged group had a higher hemoglobin increase compared to loose iron group.

Trial registration

No.PACTR201707002436264(20 /07/ 2017).
Improved urine DNA methylation panel for early bladder cancer detection
Authors: Fang Qixun , Zhang Xu , Nie Qing , Hu Jianqiang , Zhou Shujun , Wang Chaojun
Published: March 2022

Background

Bladder cancer is one of the most common malignancies but the corresponding diagnostic methods are either invasive or limited in specificity and/or sensitivity. This study aimed to develop a urine-based methylation panel for bladder cancer detection by improving published panels and validate performance of the new panel with clinical samples.

Methods

Related researches were reviewed and 19 potential panels were selected. RRBS was performed on a cohort with 45 samples to reassess these panels and a new panel inherited best markers was developed. The new panel was applied with qMSP platform to 33 samples from the RRBS cohort and the results were compared to those of RRBS. Lastly, another larger cohort with 207 samples was used to validate new panel performance with qMSP.

Results

Three biomarkers (PCDH17, POU4F2 and PENK) were selected to construct a new panel P3. P3 panel achieved 100% specificity and 71% sensitivity with RRBS in corresponding cohort and then showed a better performance of 100% specificity and 84% sensitivity with qMSP platforms in a balanced cohort. When validated with 207-sample cohort, P3 with qMSP showed a performance of 97% specificity and 87% sensitivity which was modestly improved compared to the panels it derided from.

Conclusions

Overall, the P3 panel achieved relatively high sensitivity and accuracy in bladder cancer detection.
Orbital subperiosteal hematoma associated with frontal and ethmoidal sinusitis
Authors: Kim Jonghyun , Lee Hyunkyu , Baek Sehyun
Published: March 2022

Background

We report a rare case of orbital subperiosteal hematoma associated with frontal and ethmoidal sinusitis. Common concerns involving the orbital subperiosteal space include abscess, hematoma and tumor.

Case presentation

A patient presented to our clinic with periorbital swelling and limited extraocular muscle movement in her left eye. Computed tomography revealed a superior subperiosteal mass with frontal and ethmoidal sinusitis. We diagnosed the patient with subperiosteal hematoma and surgical evacuation was performed via superior orbitotomy. Brown serous discharge was drained and biopsy demonstrated fibrin clots. The final diagnosis was orbital subperiosteal hematoma and the patient was discharged with symptoms resolved.

Conclusion

Orbital subperiosteal hematoma is difficult to distinguish from abscess owing to its rarity and similar presentation. Computed tomography is helpful in diagnosis, and surgical evacuation during the early stages is essential to achieving a good outcome.
Half-life time prediction of developing first-line antiretroviral treatment failure and its risk factors among TB and HIV co-infected children in Northwest Ethiopia; multi setting historical follow-up study
Authors: Chanie Ermias Sisay , Muche Achenef Asmamaw , Gobeza Mengistu Berhanu , Alemu Eshetie Molla , Addis Wondimnew Desalegn , Azanaw Melkalem Mamuye , Gebremariam Alemayehu Digssie , Tesfa Desalegn , Engidaw Melaku Tadege , Atikilit Getaneh , AbebawTiruneh Sofonyas , Arage Getachew
Published: March 2022

Background

Even though treatment failure is higher among TB and HIV infected children in a resource-limited setting, there is no prior evidence in general and in the study area in particular. Hence, this study was aimed at determining the half-life time prediction of developing first-line antiretroviral treatment failure and its risk factors among TB and HIV co-infected children.

Methods

A historical follow-up study was employed among 239 TB and HIV co-infected children from January 2010-December 2020. The data was entered into Epi data version 4.2.2 and exported to STATA 14.0 Software for analysis. The Kaplan-Meier plot was used to estimate the half-life time to develop treatment failure. The required assumption was fulfilled for each predictor variable. Additionally, those variables having a p-value ≤0.25 in the bivariable analysis were fitted into a multivariable Cox-proportional hazards regression model. P-value, < 0.05 was used to declare a significant association.

Results

A total of 239 TB and HIV co-infected children were involved in this study. The overall half-life time to develop first treatment failure was found to be 101 months, with a total of 1027.8 years’ follow-up period. The incidence rate and proportion of developing first-line treatment failure were 5.5 per 100 PPY (Person-Year) [CI (confidence interval): 3.7, 6.9] 100 PPY and 23.8% (CI; 18.8, 29.7) respectively. Factors such as hemoglobin 10 mg/dl [AHR (Adjusted Hazard Ratio): 3.2 (95% CI: 1.30, 7.73), severe acute malnutrition [AHR: 3.8 (95% CI: 1.51, 79.65), World Health Organization stage IV [AHR: 2.4 (95% CI: 1.15, 4.93)], and cotrimoxazole prophylaxis non user [AHR: 2.3 (95% CI: 1.14, 4.47)] were found to be a risk factor to develop treatment failure.

Conclusion

In this study, the half-life time to develop first-line treatment failure was found to be very low. In addition, the incidence was found to be very high. The presence of hemoglobin 10 mg/dl, severe acute malnutrition, World Health Organization stage, and non-use of cotrimoxazole prophylaxis were discovered to be risk factors for treatment failure. Further prospective cohort and qualitative studies should be conducted to improve the quality of care in paediatric ART clinics to reduce the incidence or burden of first line treatment failure among TB and HIV co-infected children.
Exploring social emotion processing in autism: evaluating the reading the mind in the eyes test using network analysis
Authors: Li Tai-Shan , Gau Susan Shur-Fen , Chou Tai-Li
Published: March 2022

Background

Features of autism spectrum disorder (ASD) include difficulties in processing and interpreting socioemotional information. The "Reading the Mind in the Eyes" test (RMET) is a validated measurement for processing socioemotional ability. However, previous RMET studies did not explore patterns of incorrect answers and the emotional valence of the test items. This study used the Taiwanese version of the RMET and the network analysis methods to examine the differences in underlying mechanisms of socioemotional processes between 30 males with autism spectrum disorder (ASD) (mean age = 18 years) and 30 healthy control males (mean age = 17 years). For each test item, a picture of a person's eyes and partial face was shown with four words describing the emotional status on picture corners. Participants were instructed to choose one of the four words that best matched the person's thinking or feeling. We further classified the words into three valences of emotional categories to examine socioemotional processes.

Results

Our results showed that ASD males performed poorer on the RMET than the controls. ASD males had higher network density and in-degree scores, especially in negative words, than control males.

Conclusions

The findings suggest that males with ASD might have deficits in mapping the best emotional concept words to the target item, especially for processing negative emotion.
“It’s how we get to know each other”: Substance use, connectedness, and sexual activity among men who have sex with men who are living with HIV
Authors: Stanton Amelia M. , Wirtz Megan R. , Perlson Jacob E. , Batchelder Abigail W.
Published: March 2022

Background

Among MSM, substance use increases risk for acquiring HIV and is associated with sub-optimal engagement in HIV-related care. Most research related to substance use and sexual activity among MSM focuses on identifying and reducing risk of HIV acquisition and transmission rather than pleasure and agency. However, substance use may also facilitate sexual pleasure and build community, which could be particularly meaningful for individuals who cope with intersecting stigmas related to the disease, sexual identity, and drug use.

Methods

To explore the ways in which substance use both promotes and hinders positive sexual expression and healthy sexual relationships, we conducted a secondary analysis of 33 semi-structured qualitative interviews with MSM living with HIV who were poorly engaged in care and reported recent substance use.

Results

Thematic analysis revealed that substance use was perceived as: (1) a potential pathway to intimacy and enhanced sexual experiences; (2) a tool to help access partners and gain entry to a community; and (3) a source of empowerment, though some noted that it sometimes came at the cost of sexual disempowerment and unbalanced relationships.

Conclusions

Clinically, our results suggest that the complex motivations for substance use during sexual activity need to be carefully considered and discussed with patients, especially when attempting to decrease problematic use as a pathway to improved HIV self-care.
Modified posterior approach of the knee in patients with diffuse pigmented Villonodular synovitis: case series of a single Institution’s experience
Authors: Wei Yi-Ping , Yang Shan-Wei
Published: March 2022

Background

Diffuse pigmented villonodular synovitis (DPVNS) is a challenging tumor-like disorder that mainly occurs in the anterior aspect of the knee joint. The growth may sometimes extend to the posterior knee joint. Surgical excision is the mainstream treatment for DPVNS, and the posterior approach of tumor excision is adopted when the dominant tumor shows posterior extension. However, the optimal surgical approach over the posterior knee remains unknown.

Methods

Patients with DPVNS of the knee joint who received the posterior approach of synovectomy from 1995 to 2019 were retrospectively reviewed to describe the modified separate posterior (SP) approaches, and evaluate the treatment outcomes in a case series of DPVNS knees. The results of the SP approach was also compared with those of traditional direct posterior (DP) approach. Postoperative functional outcomes were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) standardized questionnaire and clinician-completed Musculoskeletal Tumor Society (MSTS) functional rating system at outpatient department.

Results

A total of 20 DPVNS knees were included. Thirteen patients who received SP approaches were included in the SP group, while seven patients who received the DP approach were included in the DP group. The median follow-up times were 5.7 years (IQR, 2-8.8) in the SP group and 3 years (IQR, 2-5.3) in the DP group. Both groups showed satisfactory safety. The SP group presented higher postoperative mean WOMAC (91.23 ± 7.20) and mean MSTS (24.23 ± 2.68) than the DP group (mean WOMAC: 76.00 ± 16.57; mean MSTS: 22.43 ± 4.69). The Wilcoxon signed-rank test was use to compare preoperative and postoperative range of motion (ROM) for each group. The significant difference in SP group (p = 0.004) was found whilep = 0.131 in DP group.

Conclusions

The SP approach provides an effective approach with satisfactory outcomes for the surgical treatment of DPVNS knees.
Periprosthetic femoral fractures in Total Hip Arthroplasty (THA): a comparison between osteosynthesis and revision in a retrospective cohort study
Authors: Scalici Gianluca , Boncinelli Debora , Zanna Luigi , Buzzi Roberto , Antonucci Laura , Di Maida Fabrizio , De Biase Pietro
Published: March 2022

Background

Periprosthetic femoral fractures are challenging complications of hip arthroplasty. They are supposed to be a rare complication, but their incidence is rapidly increasing. Surgical treatment aims to achieve early mobilization and avoid the complications of prolonged bed rest. Aim of this study is to evaluate the clinical outcomes of surgical treatment comparing two surgical approaches: revision arthroplasty (RA) versus open reduction and internal fixation (ORIF).

Methods

Authors retrospectively reviewed a series of 117 patients with total hip arthroplasty treated for periprosthetic femur fractures in the period between January 2013 and March 2018 at a single tertiary referral center. Of these, 70 patients satisfied strict inclusion criteria. Patients were classified according to the Unified Classification System (UCS) and distributed in two groups according to surgical treatment. Clinical outcomes were assessed using the Oxford Hip recorded preoperatively and post operatively, Barthel Score, CIRS score (Cumulative illness rating scale), type of fracture and post-operative complications with a minimum follow up of 1 year.

Results

Nominal univariate statistical analysis revealed significant differences between the post and pre-operative Oxford Hip Score (Δ Oxford) and the surgical treatment (p = 0.008) and CIRS score (p = 0.048). Moreover, we observed a significant relationship between type of treatment and type of fracture (p = 0.0001). Multivariate analyses revealed that CIRS score was independently associated with Oxford Score improvement after surgery (p = 0.024).

Conclusions

Data from this case series confirmed that surgical treatment was correlated to type of fracture, according to UCS classification. Patients treated by RA had a better functional outcome than patients treated with ORIF, but these results are strongly influenced from the patients’ age, Barthel index and CIRS score. Also, authors found a correlation between functional outcome and comorbidities evaluated by CIRS score. Based on these data we suggest a multimodal approach to these patients, like those used for proximal femoral fractures.
Nine-year-long complex humeral nonunion salvaged by distraction osteogenesis technique: a case report and review of the literature
Authors: Jia Qiyu , Liu Yanshi , Alimujiang Abudusalamu , Guo Jian , Chen Dongsheng , Wang Yingbo , Yusufu Aihemaitijiang , Ma Chuang
Published: March 2022

Background

Humeral nonunion with significant bone loss or shortening is uncommon and poses a complex clinical problem. We present a case of humeral nonunion with a large segmental bone defect treated with the distraction osteogenesis technique and remedy the radial nerve palsy produced during distraction osteogenesis by forearm tendon transfers. The reconstruction of upper limb function was achieved with satisfactory results. This case provides a referenceable alternative method for repairing large segmental bone defects due to complex nonunion of the upper extremity, as well as a remedy in the unfortunate event of radial nerve palsy, providing a reference and lessons learned for the treatment of similar cases and the management of possible complications.

Case presentation

A 31-year-old male patient experienced 9 years of hypertrophic nonunion due to an unreliable internal fixation. The radiographs showed the absence of bone bridging between the two fragments, loosening of the screws, and extensive osteolysis around the internal screws. The patient was treated with distraction osteogenesis. At the end of the distraction period, the patient unfortunately developed right radial nerve paresis, which was salvaged by forearm tendon transplantation, and finally reconstructed hand function and achieved bone union of the humerus.

Conclusion

Distraction osteogenesis, although not a panacea for all humeral nonunions with significant segmental bone loss, does offer a viable salvage procedure in this unusual and often complex clinical problem. When irreversible radial nerve palsy occurs during distraction, forearm tendon transfers can have a good clinical effect.
Comparison of two invasive non-surgical treatment options for uterine myomas: uterine artery embolization and magnetic resonance guided high intensity focused ultrasound—systematic review
Authors: Yerezhepbayeva Madina , Terzic Milan , Aimagambetova Gulzhanat , Crape Byron
Published: March 2022

Background

Uterine Artery Embolization (UAE) and Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) are two noninvasive treatments for uterine leiomyoma.

Methods

This systematic review, following PRISMA guidelines, analyzed the effectiveness of two treatments by comparing percent fibroid volume shrinkage immediately after the procedure and after 3, 6, 12 and 24 months of follow-up and also assessed and compared common complications following treatment. The search utilized Science Direct, PubMed, MEDLINE, Google Scholar and BioMed Central databases, selecting manuscripts published during the period 2000 and 2020. Studies with premenopausal patients with previous treatments for uterine leiomyoma and/or with other pelvic diseases were excluded.

Results

Twenty-nine papers satisfied inclusion and exclusion criteria. Results were pooled and stratified by treatment and follow-up time. Weighted fibroid volume percent shrinkage after UAE was statistically significantly greater than MRgHIFU at 6, 12, and 24 months follow-up times. However, UAE had statistically significantly more complications, such as pain, nausea and vomiting. However, this study cannot conclude that UAE is more effective than MRgHIFU due to confounding factors.
Network pharmacology-based predictions of active components and pharmacological mechanisms of Artemisia annua L. for the treatment of the novel Corona virus disease 2019 (COVID-19)
Authors: Tang Yexiao , Li Xiaobo , Yuan Yueming , Zhang Hongying , Zou Yuanyuan , Xu Zhiyong , Xu Qin , Song Jianping , Deng Changsheng , Wang Qi
Published: March 2022

Background

Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19.

Methods

Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19.

Results

In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua’s potentially active compounds and targets associated with them that act against COVID-19.

Conclusions

These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.
Moral distress - a threat to dementia care? A qualitative study of nursing staff members’ experiences in long-term care facilities
Authors: Midtbust May Helen , Gjengedal Eva , Alnes Rigmor Einang
Published: March 2022

Background

Dementia is a public health priority worldwide due to its rapidly increasing prevalence and poses challenges with regard to providing proper care, including end-of-life care. This study is part of a research project about nursing staff members’ experiences with providing palliative care for people with severe dementia in long-term care facilities. In an earlier study, we found that structural barriers that complicated the provision of palliative care led to moral distress among nursing staff. In this study, we performed a secondary analysis of the same data set to gain a deeper understanding of nursing staff members experiences of moral distress while providing palliative care for residents with severe dementia in long-term care facilities.

Methods

A qualitative, descriptive design was used. Data were collected during in-depth interviews with 20 nursing staff members from four Norwegian long-term care facilities. Content previously identified as moral distress was reanalysed by thematic text analysis, as described by Braun and Clarke, to gain a deeper understanding of the phenomenon.

Results

The nursing staff members’ experiences of moral distress were generally of two types: those in which nursing staff members felt pressured to provide futile end-of-life treatment and those in which they felt that they had been prevented from providing necessary care and treatment.

Conclusion

The findings indicate that nursing staff members’ experiences of moral distress were related to institutional constraints such as time limitations and challenging prioritizations, but they were more often related to value conflicts. Nursing staff members experienced moral distress when they felt obligated to provide care and treatment to residents with severe dementia that conflicted with their own values and knowledge about good palliative care. Both education interventions focused on improving nursing staff members’ skills regarding communication, ethical judgement and coping strategies; in addition, supportive and responsive leadership may have significant value with regard to reducing moral distress. Our findings indicate a need for further research on interventions that can support nursing staff members dealing with ethical conflicts in providing palliative care to residents with dementia.
Network analysis of atherosclerotic genes elucidates druggable targets
Authors: Banik Sheuli Kangsa , Baishya Somorita , Das Talukdar Anupam , Choudhury Manabendra Dutta
Published: March 2022

Background

Atherosclerosis is one of the major causes of cardiovascular disease. It is characterized by the accumulation of atherosclerotic plaque in arteries under the influence of inflammatory responses, proliferation of smooth muscle cell, accumulation of modified low density lipoprotein. The pathophysiology of atherosclerosis involves the interplay of a number of genes and metabolic pathways. In traditional translation method, only a limited number of genes and pathways can be studied at once. However, the new paradigm of network medicine can be explored to study the interaction of a large array of genes and their functional partners and their connections with the concerned disease pathogenesis. Thus, in our study we employed a branch of network medicine, gene network analysis as a tool to identify the most crucial genes and the miRNAs that regulate these genes at the post transcriptional level responsible for pathogenesis of atherosclerosis.

Result

From NCBI database 988 atherosclerotic genes were retrieved. The protein–protein interaction using STRING database resulted in 22,693 PPI interactions among 872 nodes (genes) at different confidence score. The cluster analysis of the 872 genes using MCODE, a plug-in of Cytoscape software revealed a total of 18 clusters, the topological parameter and gene ontology analysis facilitated in the selection of four influential genes viz., AGT, LPL, ITGB2, IRS1 from cluster 3. Further, the miRNAs (miR-26, miR-27, and miR-29 families) targeting these genes were obtained by employing MIENTURNET webtool.

Conclusion

Gene network analysis assisted in filtering out the 4 probable influential genes and 3 miRNA families in the pathogenesis of atherosclerosis. These genes, miRNAs can be targeted to restrict the occurrence of atherosclerosis. Given the importance of atherosclerosis, any approach in the understanding the genes involved in its pathogenesis can substantially enhance the health care system.
The relation between age and airway epithelial barrier function
Authors: de Vries M. , Nwozor K. O. , Muizer K. , Wisman M. , Timens W. , van den Berge M. , Faiz A. , Hackett T.-L. , Heijink I. H. , Brandsma C. A.
Published: March 2022

Background

The prevalence of age-associated diseases, such as chronic obstructive pulmonary disease (COPD), is increasing as the average life expectancy increases around the world. We previously identified a gene signature for ageing in the human lung which included genes involved in apical and tight junction assembly, suggesting a role for airway epithelial barrier dysfunction with ageing.

Aim

To investigate the association between genes involved in epithelial barrier function and age both in silico and in vitro in the airway epithelium.

Methods

We curated a gene signature of 274 genes for epithelial barrier function and tested the association with age in two independent cohorts of bronchial brushings from healthy individuals with no respiratory disease, using linear regression analysis (FDR < 0.05). Protein–protein interactions were identified using STRING©. The barrier function of primary bronchial epithelial cells at air–liquid interface and CRISPR–Cas9-induced knock-down of target genes in human bronchial 16HBE14o-cells was assessed using Trans epithelial resistance (TER) measurement and Electric cell-surface impedance sensing (ECIS) respectively.

Results

In bronchial brushings, we found 55 genes involved in barrier function to be significantly associated with age (FDR < 0.05). EPCAM was most significantly associated with increasing age and TRPV4 with decreasing age. Protein interaction analysis identified CDH1, that was negatively associated with higher age, as potential key regulator of age-related epithelial barrier function changes. In vitro, barrier function was lower in bronchial epithelial cells from subjects > 45 years of age and significantly reduced in CDH1-deficient 16HBE14o-cells.

Conclusion

The significant association between genes involved in epithelial barrier function and age, supported by functional studies in vitro, suggest a role for epithelial barrier dysfunction in age-related airway disease.
Factors influencing health workers’ compliance with outpatient malaria ‘test and treat’ guidelines during the plateauing performance phase in Kenya, 2014–2016
Authors: Amboko Beatrice , Stepniewska Kasia , Machini Beatrice , Bejon Philip , Snow Robert W. , Zurovac Dejan
Published: March 2022

Background

Health workers’ compliance with outpatient malaria ‘test and treat’ guidelines has improved since 2010 but plateaued from 2014 at suboptimal levels in Kenya. This study examined the factors associated with high but suboptimal compliance levels at facilities with available malaria tests and drugs.

Methods

Data from four national, cross-sectional health facility surveys undertaken between 2014 and 2016 in Kenya were analysed. Association between 31 factors and compliance with malaria testing (survey range (SR): 65–69%) and no anti-malarial treatment for test negative patients (SR: 90–92%) were examined using multilevel logistic regression models.

Results

A total of 2,752 febrile patients seen by 594 health workers at 486 health facilities were analysed. Higher odds of malaria testing were associated with lake endemic (aOR = 12.12; 95% CI: 5.3–27.6), highland epidemic (aOR = 5.06; 95% CI: 2.7–9.5) and semi-arid seasonal (aOR = 2.07; 95% CI: 1.2–3.6) compared to low risk areas; faith-based (FBO)/ non-governmental organization (NGO)-owned compared to government-owned facilities (aOR = 5.80; 95% CI: 3.2–10.6); health workers’ perception of malaria endemicity as high-risk (aOR = 3.05; 95% CI: 1.8–5.2); supervision with feedback (aOR = 1.84; 95% CI: 1.2–2.9); access to guidelines (aOR = 1.96; 95% CI: 1.1–3.4); older patients compared to infants, higher temperature measurements and main complaints of fever, diarrhoea, headache, vomiting and chills. Lower odds of testing were associated with febrile patients having main complaints of a cough (aOR = 0.65; 95% CI: 0.5–0.9), a rash (aOR = 0.32; 95% CI: 0.2–0.7) or a running nose (aOR = 0.59; 95% CI: 0.4–0.9). Other factors associated with compliance with test negative results included the type of diagnostic test available at the facility, in-service training, health workers’ age, and correct knowledge of the targeted treatment policy.

Conclusions

To optimize outpatient malaria case-management, reduce testing compliance gaps and eliminate overtreatment of test negative patients, there is a need to focus on compliance within low malaria risk areas in addition to ensuring the universal and continuous availability of ‘test and treat’ commodities. Targeting of older and government health workers; dissemination of updated guidelines; and continuing with in-service training and supportive supervision with feedback is essential. Lastly, there is a need to improve health workers’ knowledge about malaria testing criteria considering their perceptions of endemicity.
Mini-XT, a miniaturized tagmentation-based protocol for efficient sequencing of SARS-CoV-2
Authors: Fuchs Marc , Radulescu Clara , Tang Miao , Mahesh Arun , Lavin Deborah , Umbreen Syed , McKenna James , Smyth Mark , McColgan Eilís , Molnar Zoltan , Baxter Chris , Skvortsov Timofey , Singh Aditi , Rogan Fiona , Miskelly Julia , Bridgett Stephen , Fairley Derek , Simpson David A.
Published: March 2022

Background

The COVID-19 pandemic has highlighted the importance of whole genome sequencing (WGS) of SARS-CoV-2 to inform public health policy. By enabling definition of lineages it facilitates tracking of the global spread of the virus. The evolution of new variants can be monitored and knowledge of specific mutations provides insights into the mechanisms through which the virus increases transmissibility or evades immunity. To date almost 1 million SARS-CoV-2 genomes have been sequenced by members of the COVID-19 Genomics UK (COG-UK) Consortium. To achieve similar feats in a more cost-effective and sustainable manner in future, improved high throughput virus sequencing protocols are required. We have therefore developed a miniaturized library preparation protocol with drastically reduced consumable use and costs.

Results

We present the ‘Mini-XT’ miniaturized tagmentation-based library preparation protocol available on protocols.io (10.17504/protocols.io.bvntn5en). SARS-CoV-2 RNA was amplified using the ARTIC nCov-2019 multiplex RT-PCR protocol and purified using a conventional liquid handling system. Acoustic liquid transfer (Echo 525) was employed to reduce reaction volumes and the number of tips required for a Nextera XT library preparation. Sequencing was performed on an Illumina MiSeq. The final version of Mini-XT has been used to sequence 4384 SARS-CoV-2 samples from N. Ireland with a COG-UK QC pass rate of 97.4%. Sequencing quality was comparable and lineage calling consistent for replicate samples processed with full volume Nextera DNA Flex (333 samples) or using nanopore technology (20 samples). SNP calling between Mini-XT and these technologies was consistent and sequences from replicate samples paired together in maximum likelihood phylogenetic trees.

Conclusions

The Mini-XT protocol maintains sequence quality while reducing library preparation reagent volumes eightfold and halving overall tip usage from sample to sequence to provide concomitant cost savings relative to standard protocols. This will enable more efficient high-throughput sequencing of SARS-CoV-2 isolates and future pathogen WGS.
Anti-obesity effects of heat-transformed green tea extract through the activation of adipose tissue thermogenesis
Authors: Im Hyeonyeong , Lee Jaewon , Kim Kyungmin , Son Yeonho , Lee Yun-Hee
Published: March 2022

Background

Adipose tissue thermogenesis is a potential therapeutic target to increase energy expenditure and thereby combat obesity. The aim of the present study was to investigate the thermogenic and anti-obesity effects of heat-transformed green tea extract (HTGT) and enzymatically modified isoquercetin (EMIQ).

Methods

Immortalized brown pre-adipocytes and C3H10T1/2 cells were used for in vitro analyses. A high-fat diet (HFD)-induced obesity mouse model and CIDEA-reporter mice were used for in vivo experiments. The effects of HTGT and EMIQ on mitochondrial metabolism were evaluated by immunoblot, mitochondrial staining, and oxygen consumption rate analyses. In vivo anti-obesity effects of HTGT and EMIQ were measured using indirect calorimetry, body composition analyses, glucose tolerance tests, and histochemical analyses.

Results

Co-treatment with HTGT and EMIQ (50 μg/mL each) for 48 h increased brown adipocyte marker and mitochondrial protein levels (UCP1 and COXIV) in brown adipocytes by 2.9-fold, while the maximal and basal oxygen consumption rates increased by 1.57- and 1.39-fold, respectively. Consistently, HTGT and EMIQ treatment increased the fluorescence intensity of mitochondrial staining in C3H10T1/2 adipocytes by 1.68-fold. The combination of HTGT and EMIQ (100 mg/kg each) increased the expression levels of brown adipocyte markers and mitochondrial proteins in adipose tissue. Two weeks of HTGT and EMIQ treatment (100 mg/kg each) led to a loss of 3% body weight and 7.09% of body fat. Furthermore, the treatment increased energy expenditure by 8.95% and improved glucose tolerance in HFD-fed mice.

Conclusions

The current study demonstrated that HTGT and EMIQ have in vivo anti-obesity effects partly by increasing mitochondrial metabolism in adipocytes. Our findings suggest that a combination of HTGT and EMIQ is a promising therapeutic agent for the treatment of obesity and related metabolic diseases.
Qualitative and quantitative evaluation of thylakoid complexes separated by Blue Native PAGE
Authors: Sárvári Éva , Gellén Gabriella , Sági-Kazár Máté , Schlosser Gitta , Solymosi Katalin , Solti Ádám
Published: March 2022

Background

Blue Native polyacrylamide gel electrophoresis (BN PAGE) followed by denaturing PAGE is a widely used, convenient and time efficient method to separate thylakoid complexes and study their composition, abundance, and interactions. Previous analyses unravelled multiple monomeric and dimeric/oligomeric thylakoid complexes but, in certain cases, the separation of complexes was not proper. Particularly, the resolution of super- and megacomplexes, which provides important information on functional interactions, still remained challenging.

Results

Using a detergent mixture of 1% (w/V)n-dodecyl-β-d-maltoside plus 1% (w/V) digitonin for solubilisation and 4.3–8% gel gradients for separation as methodological improvements in BN PAGE, several large photosystem (PS) I containing bands were detected. According to BN(/BN)/SDS PAGE and mass spectrometry analyses, these PSI bands proved to be PSI-NADH dehydrogenase-like megacomplexes more discernible in maize bundle sheath thylakoids, and PSI complexes with different light-harvesting complex (LHC) complements (PSI-LHCII, PSI-LHCII*) more abundant in mesophyll thylakoids of lincomycin treated maize. For quantitative determination of the complexes and their comparison across taxa and physiological conditions, sample volumes applicable to the gel, correct baseline determination of the densitograms, evaluation methods to resolve complexes running together, calculation of their absolute/relative amounts and distribution among their different forms are proposed.

Conclusions

Here we report our experience in Blue/Clear-Native polyacrylamide gel electrophoretic separation of thylakoid complexes, their identification, quantitative determination and comparison in different samples. The applied conditions represent a powerful methodology for the analysis of thylakoid mega- and supercomplexes.
Primary immune regulatory disorders: Undiagnosed needles in the haystack?
Authors: Flinn Aisling M. , Gennery Andrew R.
Published: March 2022

Primary Immune Regulatory Disorders (PIRD) describe a group of conditions characterized by loss of normal inflammatory control and immune tolerance mechanisms, with autoimmunity as a predominant clinical feature. PIRD can arise due to defects in the number or function of regulatory T-lymphocytes, defects in the immune mechanisms required to ‘turn off’ inflammation such as in perforin-dependent cytotoxicity or alterations in cytokine signalling pathways. Diagnosis of PIRD is a significant challenge to physicians due to their rarity, complexity, and diversity in clinical manifestations. Many of these individual conditions lack a genotype–phenotype correlation and display incomplete penetrance. However, establishing a diagnosis is integral in optimizing patient management, including the use of individualized treatment approaches. Increasing awareness among physicians is necessary as patients are likely to present to different subspecialties. Due to the rarity of these conditions, worldwide collaboration and data-sharing is essential to improve our knowledge of the clinical spectrum and disease course in PIRD, and to optimize therapeutic strategies including identification of which patients can benefit from hematopoietic stem cell transplant.
3q27.1 microdeletion causes prenatal and postnatal growth restriction and neurodevelopmental abnormalities
Authors: Barua Subit , Pereira Elaine M. , Jobanputra Vaidehi , Anyane-Yeboa Kwame , Levy Brynn , Liao Jun
Published: March 2022

Background

Overlapping microdeletions of chromosome 3q26-3q28 have been reported in eight individuals. The common phenotype observed in these individuals include intrauterine growth restriction, short stature, microcephaly, feeding difficulties, facial dysmorphisms, limb abnormalities and developmental delay. The most striking clinical features shared among all reported cases is prenatal and postnatal growth restriction and neurodevelopmental abnormalities.

Case presentation

We identified two additional individuals with overlapping deletions and shared clinical features by high-resolution SNP oligonucleotide microarray, and refined the smallest region of overlap (SRO) to a 1.2 Mb genomic location in chromosome 3q27.1 by reviewing and comparing all published cases. We evaluated the SRO using ACMG/ClinGen current recommendations for classifying copy number variants (CNVs), and discussed the contribution of the genes deleted in the SRO to the abnormal phenotype observed in these individuals.

Conclusions

This study provides further evidence supporting the existence of a novel 3q27.1 microdeletion syndrome and suggests that haploinsufficiency of potential candidate genes, DVL3, AP2M1, and PARL in the SRO in 3q27.1 is responsible for the phenotype.