bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy
Authors: Zhao Shankun , Wu Weizhou , Lin Xuezheng , Shen Maolei , Yang Zhenyu , Yu Sicong , Luo Yu
Published: May 2022

Vital organ injury is one of the leading causes of global deaths. Accumulating studies have demonstrated that dexmedetomidine (DEX) has an outstanding protective effect on multiple organs for its antiinflammatory and antiapoptotic properties, while the underlying molecular mechanism is not clearly understood. Autophagy, an adaptive catabolic process, has been found to play a crucial role in the organ-protective effects of DEX. Herein, we present a first attempt to summarize all the evidence on the proposed roles of autophagy in the action of DEX protecting against vital organ injuries via a comprehensive review. We found that most of the relevant studies (17/24, 71%) demonstrated that the modulation of autophagy was inhibited under the treatment of DEX on vital organ injuries (e.g. brain, heart, kidney, and lung), but several studies suggested that the level of autophagy was dramatically increased after administration of DEX. Albeit not fully elucidated, the underlying mechanisms governing the roles of autophagy involve the antiapoptotic properties, inhibiting inflammatory response, removing damaged mitochondria, and reducing oxidative stress, which might be facilitated by the interaction with multiple associated genes (i.e., hypoxia inducible factor-1α, p62, caspase-3, heat shock 70 kDa protein, and microRNAs) and signaling cascades (i.e., mammalian target of rapamycin, nuclear factor-kappa B, and c-Jun N-terminal kinases pathway). The authors conclude that DEX hints at a promising strategy in the management of vital organ injuries, while autophagy is crucially involved in the protective effect of DEX.
A database for retrieving information on SARS-CoV-2 S protein mutations based on correlation network analysis
Authors: Ogata Yoshiyuki , Kitayama Ruri
Published: May 2022

Background

Over a million genomes and mutational analyses of SARS-CoV-2 are available in public databases, which reveal the phylogenetic tree of the virus. Although these data have enabled scientists to closely track the evolution and transmission dynamics of the virus at global and local scales, the Mu variant, recently identified in infections in South America, shows an unusual combination of mutations, and it is difficult to visualize these atypical characteristics in public databases based on a phylogenetic tree.

Results

The Vcorn SARS-CoV-2 database was constructed to provide information on COVID-19 infections and mutations in the S protein of the virus based on correlation network analysis. A correlation network was constructed using the recall index of one mutation to another mutation. The network includes several network modules in which nodes represent mutations and are tightly connected to each other. Individual network modules contain mutations of single variants, such as the alpha and delta variants. In the network constructed to emphasize mutations of the Mu variant using the database, the mutations were found to be located in multiple network modules, indicating that the mutations of the variant may have originated from multiple variants or be located at a basal position with a high frequency of mutation.

Conclusions

Vcorn SARS-CoV-2 provides information on COVID-19 and S protein mutations of SARS-CoV-2 via correlation network analysis. The network based on the analysis illustrates the unusual S protein mutations of the Mu variant. The database is freely available at http://www.plant.osakafu-u.ac.jp/~kagiana/vcorn/sarscov2/.
Survival-related genes are diversified across cancers but generally enriched in cancer hallmark pathways
Authors: Wang Po-Wen , Su Yi-Hsun , Chou Po-Hao , Huang Ming-Yueh , Chen Ting-Wen
Published: May 2022

Background

Pan-cancer studies have disclosed many commonalities and differences in mutations, copy number variations, and gene expression alterations among cancers. Some of these features are significantly associated with clinical outcomes, and many prognosis-predictive biomarkers or biosignatures have been proposed for specific cancer types. Here, we systematically explored the biological functions and the distribution of survival-related genes (SRGs) across cancers.

Results

We carried out two different statistical survival models on the mRNA expression profiles in 33 cancer types from TCGA. We identified SRGs in each cancer type based on the Cox proportional hazards model and the log-rank test. We found a large difference in the number of SRGs among different cancer types, and most of the identified SRGs were specific to a particular cancer type. While these SRGs were unique to each cancer type, they were found mostly enriched in cancer hallmark pathways, e.g., cell proliferation, cell differentiation, DNA metabolism, and RNA metabolism. We also analyzed the association between cancer driver genes and SRGs and did not find significant over-representation amongst most cancers.

Conclusions

In summary, our work identified all the SRGs for 33 cancer types from TCGA. In addition, the pan-cancer analysis revealed the similarities and the differences in the biological functions of SRGs across cancers. Given the potential of SRGs in clinical utility, our results can serve as a resource for basic research and biotech applications.
Anemia and iron deficiency in patients with atrial fibrillation
Authors: Hanna-Rivero Nicole , Tu Samuel J. , Elliott Adrian D. , Pitman Bradley M. , Gallagher Celine , Lau Dennis H. , Sanders Prashanthan , Wong Christopher X.
Published: May 2022

Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.
Sporadic foveolar-type adenoma in gastric body/antrum junction with gastritis cystica profunda
Authors: Guan Jian , Li Zhuo , Shen Guihua , Huang Wenting
Published: May 2022

Background

Sporadic gastric foveolar-type adenomas are extremely rare and are usually small, flat or slightly raised lesions that occur in the oxyntic mucosa.

Case presentation

We reported here a case of a 70-year-old female with a sporadic gastric foveolar-type adenoma occurring in the mucosa at the junction of the gastric body/antrum. The adenoma was a protruding lesion of 2 × 1.8 cm sized, causing symptoms of upper gastrointestinal bleeding, and the basal and surrounding mucosa showed pseudopyloric gland metaplasia without atrophy, intestinal metaplasia, H. pylori infection, or active inflammation. It had somatic mutations in both APC and KRAS genes.

Conclusions

This is the first reported case of a large sporadic gastric foveolar-type adenoma that occurred in the mucosa of pseudopyloric gland metaplasia and with Gastritis Cystica Profunda, which modify our understanding of the morphological features and molecular underpinnings of this type of lesion.
Effect of individually tailored nutritional counselling on protein and energy intake among older people receiving home care at risk of or having malnutrition: a non-randomised intervention study
Authors: Kaipainen Tarja , Hartikainen Sirpa , Tiihonen Miia , Nykänen Irma
Published: May 2022

Background

With ageing, food intake may decrease and lead to an insufficient nutrient intake causing protein-energy malnutrition (PEM) which is associated with adverse health effects and increased mortality. The aim of this study was to investigate the effects of individually tailored dietary counseling focused on protein intake among home care clients with PEM or at risk of developing PEM. The secondary aim was to study the intake of energy and other nutrients.

Methods

This intervention study is part of the non-randomised population-based multidisciplinary Nutrition, Oral Health and Medication study (NutOrMed study). The intervention group comprised 112 and the control group 87 home care clients (≥75 years) with PEM or risk of PEM. PEM was defined by Mini Nutritional Assessment score < 24 and/or plasma albumin < 35 g/L. The nutrients intake was assessed from 24-hour dietary recall at the baseline and after the six-month intervention. The intervention consisted of an individually tailored dietary counseling; the persons were instructed to increase their food intake with protein and energy dense food items, the number of meals and consumption of protein-, energy- and nutrient-rich snacks for six months.

Results

After the six-month nutritional intervention, the mean change in protein intake increased 0.04 g/kgBW (95% CI 0.05 to 0.2), fibre 0.8 g (95% CI 0.2 to 4.3), vitamin D 8.5 μg (95% CI 0.7 to 4.4), E 0.6 mg (95% CI 0.4 to 2.2), B12 0.7 μg (95% CI 0.02 to 2.6), folate 8.7 μg (95% CI 1.5 to 46.5), iron 0.4 mg 95% CI 0.6 to 2.4), and zinc 0.5 mg (95% CI 0.6 to 2.2) in the intervention group compared with the control group. The proportion of those receiving less than 1.0 g/kg/BW protein decreased from 67 to 51% in the intervention group and from 84 to 76% in the control group. Among home care clients with a cognitive decline (MMSE< 18), protein intake increased in the intervention group by 0.2 g/kg/BW (p = 0.048) but there was no change in the control group.

Conclusion

An individual tailored nutritional intervention improves the intake of protein and other nutrients among vulnerable home care clients with PEM or its risk and in persons with cognitive decline.

Trial registration

ClinicalTrials.gov: NCT02214758. Date of trial registration: 12/08/2014.
Early diagnosis and treatment of acute brucellosis knee arthritis complicated by acute osteomyelitis: two cases report
Authors: Wang Jie , Zhang Qiang
Published: May 2022

Background

Brucellosis is an endemic systemic infectious disease, the most common complication is bone and joint involvement. Sacroiliac joint and spinal joint are the most frequently involved sites in adults, but knee joint infection is rare, and acute infectious knee arthritis complicated by acute osteomyelitis is even extremely uncommon in adults. Here, we report two cases of acute septic knee arthritis complicated by acute osteomyelitis caused by Brucella melitensis (B. melitensis).

Case presentation

Both patients had a history of traveling in animal husbandry areas within three months. On clinical examination, their right knee joint was tender, swollen, had limited movement and an effusion was present. Imaging examination showed effusion and synovial thickening of the right knee joint, as well as subchondral bone edema of the distal femur and proximal tibia. Laboratory examination showed that the serum agglutination test (SAT) in both patients were positive (1: 640 and 1: 320) without leukocytosis, although the proportion of lymphocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) significantly increased. Both patients underwent knee joint aspiration. Real-time polymerase chain reaction (Real-time PCR) analysis of synovial fluid showed that there was B. melitensis, and blood bacterial culture was negative. We determined that two patients had acute brucellosis knee arthritis complicated by acute osteomyelitis. Antibiotic treatment was given during hospitalization consisting of doxycycline (0.1 g po bid) and rifampicin (0.6 g po qd) for six weeks, and the changes of inflammatory indexes were closely monitored. At discharge, the symptoms had completely resolved, imaging abnormalities disappeared, and inflammatory indexes returned to normal. There was no recurrence of the disease at 1-year follow-up.

Conclusion

Acute brucellosis knee arthritis complicated by acute osteomyelitis is a rare but serious complication of brucellosis in adults. There is no obvious specificity of clinical manifestation and imaging examination. Early diagnosis and treatment can prevent the occurrence of knee joint deformity and even pathological fracture. Clinicians should fully consider the possibility of brucellosis where the travel or occupational history is suggestive.
Signature of chronic hepatitis B virus infection in nails and hair
Authors: Komatsu Haruki , Inui Ayano , Odmaa Enkhtaivan , Ito Yoshinori , Hoshino Hiroki , Umetsu Shuichiro , Tsunoda Tomoyuki , Fujisawa Tomoo
Published: May 2022

Background

Hepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown.

Methods

We examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients’ fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails.

Results

Of the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for β-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients’ serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were β-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails.

Conclusions

Nails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.
Accommodative responses under various viewing conditions in surgical patients with intermittent exotropia: an institutional, retrospective study
Authors: Qi Ziyi , Du Linlin , Chen Jun , Xu Xun , He Xiangui , Qiang Jun
Published: May 2022

Purpose

To investigate the difference of spherical equivalent (SE) and pupil diameter in adult patients with intermittent exotropia (IXT) under various viewing conditions before and after surgery.

Methods

We retrospectively analyzed the medical records of 23 adult patients who underwent a surgery for IXT. The angle of deviation was measured by the prism and alternative cover test. Refractive error and pupil diameter were measured using the Grand Seiko WAM-5500 open-field autorefractor under binocular and monocular viewing conditions when patients stared at distance (6 m) and near (33 cm). Regression analyses were performed between accommodative load and the angle of deviation.

Results

Twenty-three patients (10 males, 13 females) with a mean age of 31.17±8.95 years, of whom 13 (56.5%) had the right eye as the dominant eye. The mean angle of deviation at near and at distance was 69.57±26.37 and 65.43±28.92 prism diopters respectively. There were no significant differences in accommodative response and pupil diameter between the dominant and non-dominant eyes. SE decreased when patients changed from monocular to binocular viewing, and from distant to near viewing (all P< 0.05), so as the pupil diameter (all P< 0.001). During binocular, not monocular viewing, SE was significantly greater after operation than it was before operation (P< 0.001). Accommodative load and pupillary constriction narrowed (p< 0.001) after the operation. Linear regression analysis showed a correlation between the angle of deviation at distance and accommodative load at distance (r2=0.278, p=0.010) and at near (r2=0.332, p=0.005).

Conclusion

In order to maintain ocular alignment, patients with IXT suffer a large accommodative load, which is related to the angle of deviation. Surgery helps eliminating extra accommodation.
Social support moderates the association of functional difficulty with major depression among community-dwelling older adults: evidence from LASI, 2017–18
Authors: Muhammad T. , Maurya Priya
Published: May 2022

Background

This study aimed to examine the potential independent association of functional disability with major depression and moderating effects of social support variables including marital status, living arrangement and social participation in such associations.

Methods

Data for the study were drawn from the Longitudinal Ageing Study in India (LASI) wave 1 that was collected during 2017–18 including a sample of 31,464 individuals aged 60 years and above. Descriptive statistics and results from bivariate analysis have been reported. Further, moderated multivariable logistic regression models were used to fulfil the study objective. Major depressive disorder was assessed using the scale of the Short Form Composite International Diagnostic Interview (CIDI-SF).

Results

It was found that 8.67% of older participants were depressed in this study. Older adults who had difficulty in basic activities of daily living (BADL) (15.34%), difficulty in instrumental activities of daily living (IADL) (12.06%), unmarried (10.13%), separate living (9.67%) and socially inactive (10.09) were having higher prevalence of major depression compared to their respective counterparts. The adjusted model-1 revealed that older adults who had difficulty in BADL and IADL were 2.53 times [AOR: 2.53, CI: 2.17—2.95] and 2.27 times [AOR: 2.27, CI: 1.97—2.64] more likely to have major depression than those with no difficulty in BADL and IADL respectively. Further, interaction analyses found that currently unmarried status, separate living and being socially inactive have moderation effects in the observed associations and exacerbate the likelihood of major depression among older adults who are functionally impaired.

Conclusions

The findings highlight the importance of integrating social participation in the daily life of older adults and developing initiatives that promote a healthy surrounding such as social connectedness, co-residential living and special care for those who are physically disabled to protect against late-life depression.
Design, delivery, and determinants of uptake: findings from a food hygiene behavior change intervention in rural Bangladesh
Authors: Sobhan Shafinaz , Müller-Hauser Anna A. , Huda Tarique Md. Nurul , Waid Jillian L. , Gautam Om Prasad , Gon Giorgia , Wendt Amanda S. , Gabrysch Sabine
Published: May 2022

Background

Microbial food contamination, although a known contributor to diarrheal disease and highly prevalent in low-income settings, has received relatively little attention in nutrition programs. Therefore, to address the critical pathway from food contamination to infection to child undernutrition, we adapted and integrated an innovative food hygiene intervention into a large-scale nutrition-sensitive agriculture trial in rural Bangladesh. In this article, we describe the intervention, analyze participation and uptake of the promoted food hygiene behaviors among intervention households, and examine the underlying determinants of behavior adoption.

Methods

The food hygiene intervention employed emotional drivers, engaging group activities, and household visits to improve six feeding and food hygiene behaviors. The program centered on an ‘ideal family’ competition. Households’ attendance in each food hygiene session was documented. Uptake of promoted behaviors was assessed by project staff on seven ‘ideal family’ indicators using direct observations of practices and spot checks of household hygiene conditions during household visits. We used descriptive analysis and mixed-effect logistic regression to examine changes in household food hygiene practices and to identify determinants of uptake.

Results

Participation in the food hygiene intervention was high with more than 75% attendance at each session. Hygiene behavior practices increased from pre-intervention with success varying by behavior. Safe storage and fresh preparation or reheating of leftover foods were frequently practiced, while handwashing and cleaning of utensils was practiced by fewer participants. In total, 496 of 1275 participating households (39%) adopted at least 5 of 7 selected practices in all three assessment rounds and were awarded ‘ideal family’ titles at the end of the intervention. Being an ‘ideal family’ winner was associated with high participation in intervention activities [adjusted odds ratio (AOR): 11.4, 95% CI: 5.2–24.9], highest household wealth [AOR: 2.3, 95% CI: 1.4–3.6] and secondary education of participating women [AOR: 2.2, 95% CI: 1.4–3.4].

Conclusion

This intervention is an example of successful integration of a behavior change food hygiene component into an existing large-scale trial and achieved satisfactory coverage. Future analysis will show if the intervention was able to sustain improved behaviors over time and decrease food contamination and infection.
Social factors associated with trust in the health system in northern Sweden: a cross-sectional study
Authors: Baroudi Mazen , Goicolea Isabel , Hurtig Anna-Karin , San-Sebastian Miguel
Published: May 2022

Background

Despite the importance of having trust in the health system, there is a paucity of research in this field in Sweden. The aim of this study was to estimate the level of trust in the health system and to assess the factors associated with it in northern Sweden.

Methods

A cross-sectional survey was conducted in 2014 in the four northern regions of Sweden. A total of 24 795 participants (48% response rate) aged 18 to 84 years were involved in the study. A log-binomial regression was used to measure the association between sociodemographic factors and trust in the health system.

Results

Two thirds of the participants (68.5%) reported high trust in the health system i.e. had very much or quite a lot confidence in the health system. Women had lower prevalence of trust compared to men (PR = 0.96; 95% CI = 0.94–0.98) while older participants had a higher trust compared to youth (PR = 1.11; 95% CI = 1.06–1.16). Participants with lower level of education, those who experienced economic stress, those who were born outside Sweden and those living in small municipalities also had lower prevalence of trust in the health system. Conversely, lower income was associated with higher trust (PR = 1.08; 95% CI = 1.04–1.12). Finally, a strong relationship between higher social capital (having emotional and instrumental support, horizontal trust, and higher social participation) and trust in the health system was also found.

Conclusions

Trust in the health system was moderately high in northern Sweden and strongly associated with sociodemographic and social capital factors. Trust is a complex phenomenon and a deeper exploration of the relation between trust in the health system and sociodemographic factors is needed.
Associations between burnout symptoms and social behaviour: exploring the role of acute stress and vagal function
Authors: Wekenborg Magdalena K. , Hill LaBarron K. , Grabbe Pia , Thayer Julian F. , Kirschbaum Clemens , Lindenlaub Susan , Arne Wittling Ralf , von Dawans Bernadette
Published: May 2022

Background

The study aimed to investigate the link between burnout symptoms and prosocial behaviour, as well as the role of acute stress and vagally-mediated heart rate variability (vmHRV) on this association.

Methods

Seventy men were randomly assigned to either the stress or the control condition of the Trier Social Stress Test for Groups (TSST-G). Prosocial behaviour was assessed via a social decision-making paradigm during the respective TSST-G condition.

Results

Correlation analyses revealed negative correlations between prosocial behaviour and burnout symptoms. Acute stress was also associated with reduced prosocial behaviour, whereas no interaction effects with burnout symptoms could be revealed. Exploratory analyses showed that vmHRV was negatively correlated with burnout symptoms during the social decision-making paradigm but did not mediate the link between burnout and prosocial behaviour.

Conclusion

In conclusion, we report first experimental evidence that burnout symptoms are negatively associated with prosocial behaviour. Further studies are needed to explore the causal relations.
Comparison of serum inflammatory indicators and radiographic results in MAKO robotic-assisted versus conventional total knee arthroplasty for knee osteoarthritis: a retrospective study of Chinese patients
Authors: Xu Jia-Zheng , Li Liang-Liang , Fu Jun , Xu Chi , Zhang Guo-Qiang , Chai Wei , Hao Li-Bo , Li Xiang , Chen Ji-Ying
Published: May 2022

Background

The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA).

Methods

We retrospectively analysed 65 patients with knee osteoarthritis who underwent unilateral TKA from December 2020 to November 2021 in our department, which included 34 patients who underwent MA-TKA and 31 patients who underwent CM-TKA. The tourniquet time and estimated blood loss (EBL) were compared between the two groups. Knee function was evaluated using range of motion (ROM), functional score and pain score. Leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), creatine kinase (CK), and neutrophil-to-lymphocyte ratio (NLR) were recorded at 3 time points (preoperative, and on the first and third postoperative days). The hip-knee-ankle angle (HKA) and the femoral and tibial component angles in the coronal and sagittal planes were used for postoperative radiographic evaluation.

Results

The postoperative MA-TKA group had less EBL (496.9 ± 257.8 vs. 773.0 ± 301.3 ml, p < 0.001). There was no significant difference in knee function scores at 6 weeks postoperatively (p > 0.05). IL-6 levels were significantly lower in the MA-TKA group on the 1st postoperative day (11.4 (5.2, 21.0) vs. 24.6 (86.3, 170.8), p = 0.031). This difference in inflammatory indices became more pronounced at 72 hours after the operation because CRP, ESR, IL-6, and CK values were significantly lower in the MA-TKA group on the 3rd postoperative day (72 h) (p < 0.05). Postoperative radiographic examinations performed 2 days after the MA-TKA group suggested that only 2 cases of HKA had outlier values, which was remarkably better than the 12 cases found in the CM-TKA group (5.9% vs. 38.7%, p < 0.001). The frontal femoral component was significantly closer to the expected value of 90° in the MA-TKA group (90.9 (90.5, 92.3) vs. 92.4 (91.3, 93.7), p = 0.031). The remaining imaging evaluation parameters were not significantly different between the two groups (p > 0.05).

Conclusions

In Chinese patients with OA, there was a milder systemic inflammatory response in the early postoperative period after MA-TKA compared to that of CM-TKA, as well as better radiographic outcomes. However, the tourniquet time was prolonged, and no advantages were observed in terms of functional score or pain score in the short-term follow-up.
Relapsed boyhood tibia polymicrobial osteomyelitis linked to dermatophytosis: a case report
Authors: Kong Ping , Ren Youliang , Yang Jin , Fu Wei , Liu Ziming , Li Zhengdao , He Wenbin , Wang Yunying , Zheng Zhonghui , Ding Muliang , Schwarz Edward M. , Deng Zhongliang , Xie Chao
Published: May 2022

Background

Relapsed childhood polymicrobial osteomyelitis associated with dermatophytosis has not been reported in the literature.

Case presentation

Here we report on a case of a 45-year-old man who had left tibial osteomyelitis for 29 years, accompanied by skin fungal infection of the ipsilateral heel for 20 years, and underwent a second operation due to recurrence of polymicrobial infection 6 years ago. The patient had a history of injury from a rusty object, which penetrated the anterior skin of the left tibia middle segment causing subsequent bone infection, but was asymptomatic after receiving treatments in 1983. The patient was physically normal until dermatophytosis occurred on the ipsilateral heel skin in 1998. The patient complained that the dermatophytosis was gradually getting worse, and the tibial wound site became itchy, red, and swollen. The left tibial infection resurged in May 2012, leading to the patient receiving debridement and antibiotic treatment. H&E and Gram-stained histology was performed on biopsy specimens of sequestrum and surrounding inflammatory tissue. Tissue culture and microbiology examination confirmed polymicrobial infection with Staphylococcus aureus (S. aureus) and Corynebacterium and a fungus. Additionally, the patient also received potassium permanganate for dermatophytosis when he was admitted into the hospital.

Conclusions

Together with longitudinal follow-up of medical history, surgical findings, histopathological and microbiology culture evidence, we conclude that boyhood tibia polymicrobial osteomyelitis with S. aureus and Corynebacterium occurred in this patient, and the fungal activation of dermatophytosis may have led to osteomyelitis relapse.
Determining the learning curve for a novel microsurgical procedure using histopathology
Authors: Taher Amir , Chow Joanne , Kwon Min Sung , Hunter Damien , Lucewicz Ania , Samarawickrama Chameen
Published: May 2022

Purpose

Wet laboratories are becoming an increasingly important training tool as part of a push to a proficiency-based training model. We created a microsurgical wet laboratory to investigate the utility of histopathology use in assessing surgical outcomes and determine the learning curve of a novel microsurgical procedure.

Methods

A microsurgical wet laboratory was established using pig eyes to simulate the human cornea. Three novice surgeons and an experienced surgeon performed an anterior cornea lamellar dissection and the duration of the procedure was recorded. With the aid of histological analysis, the thickness and characteristics of the dissected graft was recorded. The number of attempts to complete the experiment, defined as three successful dissections with mean thickness below 100 μm, was documented.

Results

The use of histopathology was highly successful allowing in-depth analysis of the dissected graft for each attempt. Trainees reached the endpoint of the study in 21, 26 and 36 attempts (mean: 28 attempts) whilst the corneal surgeon completed the experiment in 12 attempts (p = 0.07). Mean dissection thickness decreased over time for all participants. The mean dissection time for trainees was 10.6 ± 4.2 min compared to the corneal surgeon with a mean of 8.2 ± 3.1 min (p = 0.03).

Conclusion

We propose a corneal wet laboratory model that allows for simple, efficient, and flexible microsurgical training. The use of histopathological analysis allows for careful graft analysis, providing objective feedback throughout the training exercise. Trainees demonstrated improvements in the three key aspects of the procedure: accuracy as evidenced by decreasing histological thickness, confidence by self-report and fluidity by decreasing duration of the procedure.
Health services availability and readiness moderate cash transfer impacts on health insurance enrolment: evidence from the LEAP 1000 cash transfer program in Ghana
Authors: Otieno Peter , Angeles Gustavo , Quiñones Sarah , van Halsema Vincent , Novignon Jacob , Palermo Tia ,   the LEAP 1000 Evaluation Team, Palermo Tia , de Groot Richard , Valli Elsa , Osei-Akoto Isaac , Adamba Clement , K. Darko Joseph , Darko Osei Robert , Dompae Francis , Yaw Nana , Handa Sudhanshu , Barrington Clare , Abdoulayi Sara , Angeles Gustavo , Chakrabarti Averi , Otchere Frank , J. Akaligaung Akalpa , Aborigo Raymond
Published: May 2022

Background

Expanding health insurance coverage is a priority under Sustainable Development Goal 3. To address the intersection between poverty and health and remove cost barriers, the government of Ghana established the National Health Insurance Scheme (NHIS). Government further linked NHIS with the Livelihood Empowerment Against Poverty (LEAP) 1000 cash transfer program by waiving premium fees for LEAP 1000 households. This linkage led to increased NHIS enrolment, however, large enrolment gaps remained. One potential reason for failure to enroll may relate to the poor quality of health services.

Methods

We examine whether LEAP 1000 impacts on NHIS enrolment were moderated by health facilities’ service availability and readiness.

Results

We find that adults in areas with the highest service availability and readiness are 18 percentage points more likely to enroll in NHIS because of LEAP 1000, compared to program effects of only 9 percentage points in low service availability and readiness areas. Similar differences were seen for enrolment among children (20 v. 0 percentage points) and women of reproductive age (25 v. 10 percentage points).

Conclusions

We find compelling evidence that supply-side factors relating to service readiness and availability boost positive impacts of a cash transfer program on NHIS enrolment. Our work suggests that demand-side interventions coupled with supply-side strengthening may facilitate greater population-level benefits down the line. In the quest for expanding financial protection towards accelerating the achievement of universal health coverage, policymakers in Ghana should prioritize the integration of efforts to simultaneously address demand- and supply-side factors.

Trial registration

This study is registered in the International Initiative for Impact Evaluation’s (3ie) Registry for International Development Impact Evaluations (RIDIE-STUDY-ID-55942496d53af).
Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections
Authors: Jahagirdar Sanjeevan , Morris Lorna , Benis Nirupama , Oppegaard Oddvar , Svenson Mattias , Hyldegaard Ole , Skrede Steinar , Norrby-Teglund Anna ,   INFECT Study group, Bruun Trond , Rath Eivind , Nedrebø Torbjørn , Arnell Per , Rosen Anders , Hedetoft Morten , Madsen Martin B. , Svensson Mattias , Snäll Johanna , Karlsson Ylva , Nekludov Michael , Martins dos Santos Vitor A. P. , Saccenti Edoardo
Published: May 2022

﻿Abstract

Background

Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) orStreptococcus pyogenes(mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive.

Methods

In this study, we built interactomes at both the population and individual levels consisting of host-pathogen interactions inferred from dual RNA-Seq gene transcriptomic profiles of the biopsies from NSTI patients.

Results

NSTI type-specific responses in the host were uncovered. TheS. pyogenesmono-microbial subnetwork was enriched with host genes annotated with involved in cytokine production and regulation of response to stress. The polymicrobial network consisted of several significant associations between different species (S. pyogenes,Porphyromonas asaccharolyticaandEscherichia coli) and host genes. The host genes associated withS. pyogenesin this subnetwork were characterised by cellular response to cytokines. We further found several virulence factors including hyaluronan synthase, Sic1, Isp, SagF, SagG, ScfAB-operon, Fba and genes upstream and downstream of EndoS along with bacterial housekeeping genes interacting with the human stress and immune response in various subnetworks between host and pathogen.

Conclusions

At the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed byS. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients’ phenotype.
Broad humoral and cellular immunity elicited by one-dose mRNA vaccination 18 months after SARS-CoV-2 infection
Authors: Kang Chang Kyung , Shin Hyun Mu , Choe Pyoeng Gyun , Park Jiyoung , Hong Jisu , Seo Jung Seon , Lee Yung Hie , Chang Euijin , Kim Nam Joong , Kim Minji , Kim Yong-Woo , Kim Hang-Rae , Lee Chang-Han , Seo Jun-Young , Park Wan Beom , Oh Myoung-don
Published: May 2022

Background

Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic.

Methods

We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern.

Results

A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses.

Conclusion

One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.
Red cell adenylate kinase deficiency in China: molecular study of 2 new mutations (413G > A, 223dupA)
Authors: He Sijia , Chen Hongbo , Guo Xia , Gao Ju
Published: May 2022

Background

Adenylate kinase (AK) is a monomolecular enzyme widely found in a variety of organisms. It mainly catalyses the reversible transfer of adenosine nucleotide phosphate groups and plays an important role in maintaining energy metabolism. AK deficiency is a rare genetic disorder that is related to haemolytic anaemia. Chronic haemolytic anaemia associated with AK deficiency is a rare condition, and only 14 unrelated families have been reported thus far. Moreover, only 11 mutations have been identified in theAK1gene,with only 3 cases of psychomotor impairment.

Case presentation

The patient was a 3-year-old boy with severe haemolytic anaemia and psychomotor retardation. A molecular study of the patient’sAKgene revealed 2 different mutations: a heterozygous missense mutation in exon 6 (c.413G > A) and a heterozygous frameshift mutation in exon 5 (c.223dupA). Molecular modelling analyses indicated that AK gene inactivation resulted in a lack of AK activity. The patient recovered after regular blood transfusion therapy.

Conclusions

AK1 deficiency was diagnosed on the basis of low enzymatic activity and the identification of a mutation in theAK1gene located on chromosome 9q. Here, we report the first case of moderate red cell AK1 deficiency associated with chronic nonspherocytic haemolytic anaemia (CNSHA) in China. The genetic mutations were confirmed by Sanger sequencing. The variants were classified as pathogenic by bioinformatics tools, such as ACMG/AMP guidelines, Mutation Taster, SIFT, MACP, REVEL and PolyPhen2.2. Based on our evidence and previous literature reports, we speculate that the site of theAK1gene c.413G > A (p.Arg138His) mutation may be a high-frequency mutation site and the other mutation (c.223dupA) might be related to the neuropathogenicity caused by AK1 deficiency. NGS should be a part of newborn to early childhood screening to diagnose rare and poorly diagnosed genetic diseases as early as possible.
Progressive pulmonary fibrosis in a murine model of Hermansky-Pudlak syndrome
Authors: Abudi-Sinreich Shachar , Bodine Steven P. , Yokoyama Tadafumi , Tolman Nathanial J. , Tyrlik Michal , Testa Lauren C. , Han Chen G. , Dorward Heidi M. , Wincovitch Stephen M. , Anikster Yair , Gahl William A. , Cinar Resat , Gochuico Bernadette R. , Malicdan May Christine V.
Published: May 2022

Background

HPS-1 is a genetic type of Hermansky-Pudlak syndrome (HPS) with highly penetrant pulmonary fibrosis (HPSPF), a restrictive lung disease that is similar to idiopathic pulmonary fibrosis (IPF). Hps1ep/ep (pale ear) is a naturally occurring HPS-1 mouse model that exhibits high sensitivity to bleomycin-induced pulmonary fibrosis (PF). Traditional methods of administering bleomycin as an intratracheal (IT) route to induce PF in this model often lead to severe acute lung injury and high mortality rates, complicating studies focusing on pathobiological mechanisms or exploration of therapeutic options for HPSPF.

Methods

To develop a murine model of HPSPF that closely mimics the progression of human pulmonary fibrosis, we investigated the pulmonary effects of systemic delivery of bleomycin in Hps1ep/ep mice using a subcutaneous minipump and compared results to oropharyngeal delivery of bleomycin.

Results

Our study revealed that systemic delivery of bleomycin induced limited, acute inflammation that resolved. The distinct inflammatory phase preceded a slow, gradually progressive fibrogenesis that was shown to be both time-dependent and dose-dependent. The fibrosis phase exhibited characteristics that better resembles human disease with focal regions of fibrosis that were predominantly found in peribronchovascular areas and in subpleural regions; central lung areas contained relatively less fibrosis.

Conclusion

This model provides a preclinical tool that will allow researchers to study the mechanism of pulmonary fibrosis in HPS and provide a platform for the development of therapeutics to treat HPSPF. This method can be applied on studies of IPF or other monogenic disorders that lead to pulmonary fibrosis.
SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner
Authors: Wang Xiaoyu , Lu Xiansheng , Wang Ping , Chen Qiaoyu , Xiong Le , Tang Minshan , Hong Chang , Lin Xiaowen , Shi Kaixi , Liang Li , Lin Jie
Published: May 2022

Background

Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism.

Methods

CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study.

Results

The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m6A-binding protein and that m6A modifications were enriched in DSN1 mRNA in CRC cells. Two m6A modification sites (chr20:36773619–36773620 and chr20:36773645–chr20:36773646) in the SRSF9-binding region (chr20:36773597–36773736) of DSN1 mRNA were identified. SRSF9 binds to DSN1 in an m6A motif- and dose-dependent manner. SRSF9 modulates the expression of DSN1 in CRC cells. Such expression regulation was largely impaired upon methyltransferase METTL3 knockdown. Moreover, knockdown of SRSF9 accelerated DSN1 mRNA turnover, while overexpression of SRSF9 stabilized DSN1 mRNA in CRC cells. Such stabilizing was also weakened upon METTL3 knockdown.

Conclusion

Overexpression of SRSF9 was associated with lymph node metastasis and Dukes stage in CRC. Knockdown of DSN1 eliminated the effects by SRSF9 overexpression in CRC. Our results indicated that SRSF9 functions as an m6A-binding protein (termed “reader”) by enhancing the stability of DSN1 mRNA in m6A-related manner. Our study is the first to report that SRSF9-mediated m6A recognition has a crucial role in CRC progression, and highlights SRSF9 as a potential therapeutic target for CRC management.