bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating women’s acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians: a mixed methods study
Authors: Atuhairwe Susan , Hanson Claudia , Atuyambe Lynn , Byamugisha Josaphat , Tumwesigye Nazarius Mbona , Ssenyonga Ronald , Gemzell-Danielsson Kristina
Published: November 2022

Background

Studies evaluating task sharing in postabortion care have mainly focused on women in first trimester and many lack a qualitative component. We aimed to evaluate patient acceptability of treatment of incomplete second trimester abortion using misoprostol provided by midwives compared with physicians and also gained a deeper understanding of the patients’ lived treatment experiences in Uganda.

Methods

Our mixed methods study combined 1140 structured interview data from a randomized controlled equivalence trial and in-depth interviews (n = 28) among women managed with misoprostol for second trimester incomplete abortion at 14 public health facilities in Uganda. Acceptability, our main outcome, was measured at the 14-day follow-up visit using a structured questionnaire as a composite variable of: 1) treatment experience (as expected/ better than expected/ worse than expected), and 2) satisfaction - if patient would recommend the treatment to a friend or choose the method again. We used generalized mixed effects models to obtain the risk difference in acceptable post abortion care between midwife and physician groups. We used inductive content analysis for qualitative data.

Results

From 14th August 2018 to 16th November 2021, we assessed 7190 women for eligibility and randomized 1191 (593 to midwife and 598 to physician). We successfully followed up 1140 women and 1071 (94%) found the treatment acceptable. The adjusted risk difference was 1.2% (95% CI, − 1.2 to 3.6%) between the two groups, and within our predefined equivalence range of − 5 to + 5%. Treatment success and feeling calm and safe after treatment enhanced acceptability while experience of side effects and worrying bleeding patterns reduced satisfaction.

Conclusions

Misoprostol treatment of uncomplicated second trimester incomplete abortion was equally and highly acceptable to women when care was provided by midwives compared with physicians. In settings that lack adequate staffing levels of physicians or where midwives are available to provide misoprostol, task sharing second trimester medical PAC with midwives increases patient’s access to postabortion care services.

Trial registration

ClinicalTrials.gov NCT03622073.
A scoping review of regenerative medicine in medical education
Authors: Pandya Rachita , Talib Zohray
Published: November 2022

Stem cell therapeutics and regenerative medicine have taken a strong foothold in biomedicine. However, most physicians are currently not adequately prepared to identify, refer, and deliver safe regenerative therapies. To understand this gap, we sought to characterize published literature on current physician training in regenerative medicine. Our scoping review describes current training strategies to bridge the gap and integrate such education into medical curricula for adequate training.
Has the COVID-19 pandemic affected nursing students’ career self-efficacy and professional calling? The mediating impact of professional identity
Authors: Yang Li , Xu Mengfan , Kuang Jinke , Zhou Kexin , Zhu Xuemei , Kong Lingna , QI Li , Liu Heng
Published: November 2022

Background

Professional calling (PC) is crucial for ascertaining their professional goals and fulfilling career choices in nursing students. Thus, understanding its antecedents and helping schools improve PC among nursing students is critical. This study aims to explore whether professional identity (PI), as a crucial antecedent of PC, acts as an intermediary between career self-efficacy (CSE) and professional calling during the COVID-19 pandemic.

Methods

A sample of 565 nursing students were selected by a web-based survey through convenience sampling. The study was conducted from October to November 2020. Measures of CSE, PI, and PC were assessed during the COVID-19 pandemic. We analyzed demographic data and the correlation of the research variables. The significance of the mediation effect was assessed using a bootstrap method with SPSS.

Results

CSE during the COVID-19 pandemic outbreak (r = 0. 359,p < 0. 01) and PI (r = 0. 670,p < 0. 01) were both relevant to PC among nursing students. In addition, CSE had a positive indirect effect on PC through PI (β = 0. 288,p < 0. 05).

Conclusions

Higher scores in CSE and a better PI were associated with PC in nursing students. Furthermore, a better CSE had an indirect effect on the PC of students through PI. The favorable evidence in our study confirms that nursing educators can adopt PI interventions to improve the sense of PC among nursing students.
The impact of price transparency and competition on hospital costs: a research on all-payer claims databases
Authors: Han Ahreum , Lee Keon-Hyung , Park Jongsun
Published: November 2022

Background

Public reporting has been considered effective in reducing health care costs by mitigating information asymmetry in the market as payers have incorporated publicly available information mandates into pay-for-performance programs and value-based purchasing. Therefore, hospitals have faced increasing pressures to provide price transparency. Despite the widespread promotion of healthcare transparency, the effectiveness of public reporting has not yet been sufficiently understood. This study analyzed the impact of transparency policy and competition on hospital costs by taking the state operations of all-payer claims databases (APCDs) as a case of interest.

Methods

We employed a fixed-effects regression, which allows the generation of hospital-specific effects, in accordance with the suggestion by the Hausman test. The study samples comprise nonprofit and for-profit general acute care hospitals in the United States for 2011–2017. The finalized dataset ranges from 3547 observations in 2011 to 3405 observations in 2015 after removing missing values.

Results

We found that hospitals in the states with APCDs tend to bear higher average operating expenses than those without APCDs, which may indicate that states maintaining higher healthcare expenditures are more attentive to a price transparency initiative and tend to adopt APCDs. With regard to competition, the results showed that weak market competition is significantly associated with higher operating costs, supporting the traditional competition theory. However, the combined effect of APCDs and competition did not indicate a significant association with operating expenses. Further investigation showed a continued tendency for a weak intensity of competition to be linked to lower hospital operating costs in states without APCDs. For those located in non-APCD adopted states, market consolidation helped hospitals coordinate care more effectively, economize operating costs, and enjoy economies of scale due to their large size. Similar trends did not appear in APCD-adopted states except for in 2015.

Conclusions

This study observed limited evidence of the impact of APCDs and market competition. Our findings suggest that states need to make multifaceted efforts to contain hospital costs, not solely depending on the rollout of cost information or market competition. Market concentration may lead to coordinated care or cost economization in some cases. Still, the existing literature also demonstrates some potentially harmful impacts of increased concentration in the healthcare market, such as inefficient use of resources, unilateral market power, and deterrence of innovation. The introduction of a price transparency tool may require additional policy actions that take market competition into consideration.
Sequential mixed method evaluation of the acceptability, feasibility, and appropriateness of cognitive behavioral therapy for psychosis stepped care
Authors: Kopelovich Sarah L. , Maura Jessica , Blank Jennifer , Lockwood Gloria
Published: November 2022

Background

Cognitive Behavioral Therapy for psychosis (CBTp) is recommended by national treatment guidelines yet remains widely inaccessible in the U.S. A stepped care model, favored and feasible for other scarce interventions, may improve access to CBTp.

Methods

We employed an exploratory sequential mixed method design inclusive of two distinct phases to quantitatively evaluate the acceptability, feasibility, and appropriateness of CBTp Stepped Care (CBTp-SC) among practitioners who were trained in low-intensity CBTp (Step 1), Group-Administered CBTp (Step 2), and Formulation-based CBTp (Step 3). In Phase 1, we queried respondents using the Acceptability of Intervention Measure, Intervention Appropriateness Measure, and the Feasibility of Intervention Measure to ascertain perceptions of these leading indicators of implementation success. In Phase 2, we conducted focus groups with CBTp-SC-trained practitioners (n = 10) and administrators (n = 2) from 2 of the 4 Phase 1 study sites to evaluate the theoretical assumptions of stepped care and to better understand key barriers and facilitators.

Results

Forty-six practitioners trained in all three levels of CBTp-SC completed the online survey in Phase 1. All participants were employed by a community mental health agency currently sustaining CBTp-SC. Respondents endorsed high levels of acceptability, feasibility, and appropriateness for the CBTp-SC model. We found evidence to suggest that licensed practitioners and Step 3 practitioners perceived formulation-based CBTp as more appropriate for their clients. In Phase 2, six themes emerged which affirmed the utility of the model for stakeholders, supported stepped care theoretical assumptions, and revealed key areas for improvement.

Conclusions

Early adopters of CBTp-SC in the U.S. perceive it to be acceptable, feasible, and appropriate in community mental health care settings. Practitioners and administrators identified training and implementation barriers, including the importance of organizational readiness, a CBTp coordinator role, and a desire to adapt the intervention. These early findings will facilitate iterative refinement of the stepped care model for U.S. public behavioral health agencies. Additional research is needed to explore perceptions and clinical outcomes among CBTp service users.
New efficient meta-fermentation process for lactic acid production from municipal solid waste
Authors: Acedos Miguel G. , Gómez-Pérez Paz , Espinosa Tamara , Abarca Christian , Ibañez Bernat , Ruiz Begoña
Published: November 2022

Background

The global market for lactic acid is witnessing growth on the back of increasing applications of lactic acid for manufacturing polylactic acid. Indeed, the lactic acid market is expected to reach 9.8 billion US dollars by 2025. The new concept of meta-fermentation has been proposed in recent years as an alternative to fermentation with pure cultures, due to multiple advantages such as lower susceptibility to contamination, no need for sterilization of culture media or lower raw material costs. However, there are still challenges to overcome to increase the conversion efficiency, decrease formation of by-products and facilitate fermentation control. In this context, the purpose of the study was to develop a robust meta-fermentation process to efficiently produce lactic acid from the OFMSW, stable at pre-industrial scale (1500 L). To maximize lactic acid production, operating conditions (pH, HRT) were modified, and a novel bioaugmentation strategy was tested.

Results

A LAB-rich inoculum was generated with LAB isolated from the digestate and grown in the laboratory with MRS medium. After feeding this inoculum to the digester (bioaugmentation), lactic acid accumulation up to 41.5 gO2/L was achieved under optimal operating conditions. This corresponds to more than 70% of the filtered COD measured in the digestate. The amount of lactic acid produced was higher than the volatile fatty acids under all feeding strategies applied.

Conclusions

The operating conditions that enhanced the production of lactic acid from mixed cultures were 55ºC, 2 days HRT and pH 4.8–5.7, with pH-control once a day. The bioaugmentation strategy improved the results obtained in the prototype without applying reinoculation. Lactic acid was the main product along with other carboxylic acids. Further improvements are needed to increase purity as well as lactic acid concentration to reach economic feasibility of the whole process (digestion of OFMSW and downstream).
Insight into carbapenem resistance and virulence of Acinetobacter baumannii from a children’s medical centre in eastern China
Authors: Zhu Yunfen , Zhang Xin , Wang Yunzhong , Tao Yunzhen , Shao Xuejun , Li Yang , Li Wei
Published: November 2022

Carbapenem-resistant Acinetobacter baumannii (CRAB) appeared more frequently in children and caused a great threat to global public health. It is urgent to investigate the carbapenem resistance and virulence of CRAB for clinicians to choose appropriate antibiotics. A retrospective study of 77 nonduplicated CRAB isolates was conducted. The carbapenem resistance and virulence genes were characterized by polymerase chain reaction (PCR) and gel electrophoresis. In the present study, A. baumannii mainly came from the intensive care unit and was mostly isolated from sputum samples. The carbapenem resistant rate of A. baumannii in 2018–2020 increased significantly compared with that in 2016–2017. All isolates had carbapenem resistant genes. They were highly resistant to a variety of antibiotics but were relatively sensitive to fluoroquinolones and tetracyclines. blaVIM and blaOXA-23 were detected in all isolates, whereas blaOXA-51, blaIMP and blaNDM were present in 98.70%, 67.53% and 31.17% of isolates, respectively. Notably, 1 isolate A. baumannii was identified as multidrug-resistant A. baumannii (MDR-AB), and 76 other extensively drug-resistance (XDR) isolates were also detected. Virulence genes were present in 100% of all isolates, including genes in the iron acquisition system (basJ), secretion systems (ompA, plcD), quorum sensing system (abaI) and biofilm formation (csuA). adeH, pgaA, and ptk were present in 98.70%, 98.70% and 94.80% of isolates, respectively. CRAB, which is prevalent in east China, carries a large number of drug resistance and virulence genes. Fluoroquinolones and tetracyclines may be effective antibiotics for the treatment of CRAB infection in children. An in-depth understanding of the resistance and virulence of CRAB is conducive to timely guiding empirical drug use and controlling infection.
Irisin protects against obesity-related chronic kidney disease by regulating perirenal adipose tissue function in obese mice
Authors: Han Fang , Kan Chengxia , Wu Di , Kuang Zengguang , Song Hongwei , Luo Youhong , Zhang Le , Hou Ningning , Sun Xiaodong
Published: November 2022

Background

Compared with typical visceral fat deposits in obesity and metabolic syndrome, perirenal adipose tissue (PRAT) dysfunction is more closely linked to obesity-related chronic kidney disease (OB-CKD). The myokine irisin reportedly promotes positive outcomes in metabolic disease. This study investigated whether irisin could reduce urinary albumin excretion and demonstrate renoprotective effects through the regulation of PRAT function in obese mice.

Methods

C57BL/6 J mice received a high-fat diet (HFD) with or without concurrent administration of irisin. Glucose tolerance, plasma levels of free fatty acids, and urinary albumin excretion were assessed, along with renal morphology. The vascular endothelial growth factor and nitric oxide in glomeruli were also analyzed, in addition to PRAT function-associated proteins.

Results

Irisin administration significantly reduced the final body weight, fat mass, and free fatty acids, without reducing PRAT mass, in HFD mice. Furthermore, irisin decreased urinary albumin excretion and attenuated both renal fibrosis and lipid accumulation. Irisin administration led to increases in PRAT function-associated proteins, including sirtuin1, uncoupling protein-1, and heme-oxygenase-1. Ex vivo treatment of PRAT and glomeruli with irisin also restored PRAT function. Finally, irisin treatment restored the vascular endothelial growth factor–nitric oxide axis.

Conclusions

Irisin attenuated metabolic disorders and protected against OB-CKD by normalizing the PRAT–kidney axis. These results suggest that agents targeting PRAT activation might be useful for treatment of OB-CKD.
Synergetic delivery of artesunate and isosorbide 5-mononitrate with reduction-sensitive polymer nanoparticles for ovarian cancer chemotherapy
Authors: Li Guang , Ling Mingjian , Yu Kunyi , Yang Wei , Liu Qiwen , He Lijuan , Cai Xuzi , Zhong Min , Mai Ziyi , Sun Rui , Xiao Yuanling , Yu Zhiqiang , Wang Xuefeng
Published: November 2022

Ovarian cancer is a highly fatal gynecologic malignancy worldwide. Chemotherapy remains the primary modality both for primary and maintenance treatments of ovarian cancer. However, the progress in developing chemotherapeutic agents for ovarian cancer has been slow in the past 20 years. Thus, new and effective chemotherapeutic drugs are urgently needed for ovarian cancer treatment. A reduction-responsive synergetic delivery strategy (PSSP@ART-ISMN) with co-delivery of artesunate and isosorbide 5-mononitrate was investigated in this research study. PSSP@ART-ISMN had various effects on tumor cells, such as (i) inducing the production of reactive oxygen species (ROS), which contributes to mitochondrial damage; (ii) providing nitric oxide and ROS for the tumor cells, which further react to generate highly toxic reactive nitrogen species (RNS) and cause DNA damage; and (iii) arresting cell cycle at the G0/G1 phase and inducing apoptosis. PSSP@ART-ISMN also demonstrated excellent antitumor activity with good biocompatibility in vivo. Taken together, the results of this work provide a potential delivery strategy for chemotherapy in ovarian cancer.

Graphical Abstract
Ophthalmic artery changes in type 2 diabetes with and without acute coronary syndrome
Authors: Wu Lan-ting , Wang Jia-lin , Wang Yan-ling
Published: November 2022

Background

Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS).

Methods

In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA.

Results

In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters.

Conclusions

This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA.
Anthocyanin improves kidney function in diabetic kidney disease by regulating amino acid metabolism
Authors: Li Yi-Xi , Lu Yong-Ping , Tang Donge , Hu Bo , Zhang Ze-Yu , Wu Hong-Wei , Fan Li-Jing , Cai Kai-Wen , Tang Chun , Zhang Yi-Qing , Hong Ling , Dong Jing-jing , Guan Bao-zhang , Yin Liang-Hong , Dai Yong , Bai Wei-bin , Zheng Zhi-Hua , Zhu Ting
Published: November 2022

Background

Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways.

Methods

To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis.

Results

We showed that the fasting blood glucose level (− 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (− 24.1 μm, P = 0.030), fibrosis score of glomerular (− 8.8%, P = 0.002), and kidney function (Cystatin C: − 701.4 pg/mL, P = 0.043; urine creatinine: − 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating.

Conclusions

Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.
Adolescent pregnancy in the time of COVID-19: what are the implications for sexual and reproductive health and rights globally?
Authors: Okeke Sylvester Reuben , Idriss-Wheeler Dina , Yaya Sanni
Published: November 2022

The COVID-19 pandemic has aggravated pre-existing challenges associated with adolescents’ sexual and reproductive health and rights (SRHR). Evolving evidence suggest that it could adversely impact the progress made towards improving sexual and reproductive health outcomes among young people. The pandemic has stalled achievements in reducing adolescent pregnancy and child marriage by reinforcing contextual and structural determinants of these reproductive health outcomes, especially among girls. The pandemic has increased disruptions to schooling, decreased access to sexual and reproductive health services and compounded pre-existing socio-economic vulnerabilities. The consequences of neglecting adolescent sexual and reproductive health services over the past 2 years, to focus on COVID-19, continue to emerge. This commentary argues for targeted and responsive approaches to adolescent SRHR that tackle preventable consequences resulting from inequities faced by adolescents globally, particularly girls.
The clinical application of customized 3D-printed porous tantalum scaffolds combined with Masquelet’s induced membrane technique to reconstruct infective segmental femoral defect
Authors: Wu Yipeng , Shi Xiangwen , Zi Shaoneng , Li Mingjun , Chen Suli , Zhang Chaoqun , Xu Yongqing
Published: November 2022

Purpose

This study mainly exams a novel treatment for infective segmental femoral defect, and we combined the 3D printed porous tantalum prosthesis and Masquelet’s induce membrane technique to reconstruct bone defect and discussed the clinical effect.

Method

The clinical research included 9 observational cases series, as a permanently implantation, the customized 3D-printed scaffolds that connected with an anatomical plate was implanted into the bone defect segment after successful formation of induced membrane, the clinical effect was evaluated by radiological exams and Paley’s bone union criteria.

Result

The personalized 3D-printed porous tantalum was, respectively, manufactured and used in 9 consecutive patients to reconstruct the infective segmental bone defect of femur, the mean defect length was 16.1 ± 2.8 cm, the mean length of follow-up was 16.9 ± 4.0 months, after 2 stage operation, there was no deep infections, refractures, sensorimotor disorder, vascular injury, ankylosis and recurrence of infection occurred in all cases. postoperative radiological exams shown stable internal fixation and osseointegration, and all these results were invariable during the follow-up time in all cases. All patients significantly obtained deformity correction and length of limb.

Conclusion

The customized 3D-printed porous tantalum prosthesis was an acceptable alternative treatment to the autogenous or allograft bone graft, the combination of the two techniques could achieve satisfactory reconstruct to infective broad bone defect in femur when other biological techniques were not suitable.
Comparison of clinical and radiological outcomes after three different surgical treatments for resistant calcifying tendinitis of the shoulder: a short-term randomized controlled trial
Authors: Verstraelen Freek , Schotanus Martijn , Klemann-Harings Steffie , Lambers Heerspink Okke , Jansen Edwin
Published: November 2022

Background

A preferable surgical treatment for patients with conservative therapy-resistant calcifying tendinitis of the shoulder is still a matter of debate. Therefore, the purpose of this study was to evaluate and compare short-term clinical and radiological results of three surgical treatment options for these patients.

Methods

A multicenter randomized trial was conducted. Sixty-nine patients were randomly assigned to receive 1. subacromial decompression (Group SAD), 2. debridement of calcifications (Group D), or 3. debridement of calcifications with SAD (Group D + SAD). Stringent inclusion and exclusion criteria were used. The primary outcome was an improvement in VAS for pain (pVAS) 6 months postoperatively. Secondary outcomes were an improvement in pVAS 6 weeks postoperatively, functional outcomes (CMS, DASH, ASES), radiological outcome, additional treatments, and complications.

Results

The improvement in pVAS was significant in all groups (p < 0.001) and did not differ between the groups after 6 months. Six weeks postoperatively, the improvement in pVAS was significantly (p = 0.03) less in Group SAD compared to Group D + SAD (16.5 mm, SD 19.3 mm vs 33.1 mm, SD 19.7 mm, respectively). The mean size of calcifications decreased significantly in all groups (p < 0.0001). In Group SAD, the size of the calcifications decreased less (p = 0.04) compared to Group D and Group D + SAD after 6 weeks. Group SAD received more additional treatments (p = 0.003) compared to Group D + SAD (9 vs 1), which were mainly subacromial cortisone injections.

Conclusions

All patient groups showed significant pain relief and an improvement in shoulder function 6 months after surgery. However, patients in Group SAD showed inferior pain relief and less improvement in DASH score after 6 weeks. Furthermore, this group required more postoperative additional treatments. No significant differences in clinical and radiological outcomes were observed between patients in Group D compared to Group D + SAD. Therefore, an arthroscopic debridement without subacromial decompression seems to be advisable for patients with therapy-resistant calcifying tendinitis of the shoulder.

Level of evidence 2, Open-Label Randomized Clinical Trial.

IRB METC Zuyderland MC. Number: 14-T-112.

Registered at trialregister.nl NL 4947.
Safe and effective off-the-shelf immunotherapy based on CAR.CD123-NK cells for the treatment of acute myeloid leukaemia
Authors: Caruso Simona , De Angelis Biagio , Del Bufalo Francesca , Ciccone Roselia , Donsante Samantha , Volpe Gabriele , Manni Simona , Guercio Marika , Pezzella Michele , Iaffaldano Laura , Silvestris Domenico Alessandro , Sinibaldi Matilde , Di Cecca Stefano , Pitisci Angela , Velardi Enrico , Merli Pietro , Algeri Mattia , Lodi Mariachiara , Paganelli Valeria , Serafini Marta , Riminucci Mara , Locatelli Franco , Quintarelli Concetta
Published: November 2022

Background

Paediatric acute myeloid leukaemia (AML) is characterized by poor outcomes in patients with relapsed/refractory disease, despite the improvements in intensive standard therapy. The leukaemic cells of paediatric AML patients show high expression of the CD123 antigen, and this finding provides the biological basis to target CD123 with the chimeric antigen receptor (CAR). However, CAR.CD123 therapy in AML is hampered by on-target off-tumour toxicity and a long “vein-to-vein” time.

Methods

We developed an off-the-shelf product based on allogeneic natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered them to express a second-generation CAR targeting CD123 (CAR.CD123).

Results

CAR.CD123-NK cells showed significant anti-leukaemia activity not only in vitro against CD123+ AML cell lines and CD123+ primary blasts but also in two animal models of human AML-bearing immune-deficient mice. Data on anti-leukaemia activity were also corroborated by the quantification of inflammatory cytokines, namely granzyme B (Granz B), interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α), both in vitro and in the plasma of mice treated with CAR.CD123-NK cells.

To evaluate and compare the on-target off-tumour effects of CAR.CD123-T and NK cells, we engrafted human haematopoietic cells (hHCs) in an immune-deficient mouse model. All mice infused with CAR.CD123-T cells died by Day 5, developing toxicity against primary human bone marrow (BM) cells with a decreased number of total hCD45+ cells and, in particular, of hCD34+CD38− stem cells. In contrast, treatment with CAR.CD123-NK cells was not associated with toxicity, and all mice were alive at the end of the experiments. Finally, in a mouse model engrafted with human endothelial tissues, we demonstrated that CAR.CD123-NK cells were characterized by negligible endothelial toxicity when compared to CAR.CD123-T cells.

Conclusions

Our data indicate the feasibility of an innovative off-the-shelf therapeutic strategy based on CAR.CD123-NK cells, characterized by remarkable efficacy and an improved safety profile compared to CAR.CD123-T cells. These findings open a novel intriguing scenario not only for the treatment of refractory/resistant AML patients but also to further investigate the use of CAR-NK cells in other cancers characterized by highly difficult targeting with the most conventional T effector cells.
A genome-wide association study of survival in patients with sepsis
Authors: Hernandez-Beeftink Tamara , Guillen-Guio Beatriz , Lorenzo-Salazar Jose M. , Corrales Almudena , Suarez-Pajes Eva , Feng Rui , Rubio-Rodríguez Luis A. , Paynton Megan L. , Cruz Raquel , García-Laorden M. Isabel , Prieto-González Miryam , Rodríguez-Pérez Aurelio , Carriedo Demetrio , Blanco Jesús , Ambrós Alfonso , González-Higueras Elena , Espinosa Elena , Muriel Arturo , Tamayo Eduardo , Martin María M. , Lorente Leonardo , Domínguez David , de Lorenzo Abelardo García , Giannini Heather M. , Reilly John P. , Jones Tiffanie K. , Añón José M. , Soro Marina , Carracedo Ángel , Wain Louise V. , Meyer Nuala J. , Villar Jesús , Flores Carlos ,   the Genetics of Sepsis (GEN-SEP) Network
Published: November 2022

Background

Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis.

Methods

This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10−8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants.

Findings

We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37–6.78], p = 4.92 × 10−8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury.

Interpretation

We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.
COVID-19-Related manuscripts: lag from preprint to publication
Authors: Drzymalla Emily , Yu Wei , Khoury Muin J. , Gwinn Marta
Published: November 2022

Objective

Preprints have had a prominent role in the swift scientific response to COVID-19. Two years into the pandemic, we investigated how much preprints had contributed to timely data sharing by analyzing the lag time from preprint posting to journal publication.

Results

To estimate the median number of days between the date a manuscript was posted as a preprint and the date of its publication in a scientific journal, we analyzed preprints posted from January 1, 2020, to December 31, 2021 in the NIH iSearch COVID-19 Portfolio database and performed a Kaplan-Meier (KM) survival analysis using a non-mixture parametric cure model. Of the 39,243 preprints in our analysis, 7712 (20%) were published in a journal, after a median lag of 178 days (95% CI: 175–181). Most of the published preprints were posted on the bioRxiv (29%) or medRxiv (65%) servers, which allow authors to choose a subject category when posting. Of the 20,698 preprints posted on these two servers, 7358 (36%) were published, including approximately half of those categorized as biochemistry, biophysics, and genomics, which became published articles within the study interval, compared with 29% categorized as epidemiology and 26% as bioinformatics.
Hospital-prepared low-dose atropine eye drops for myopia progression control using atropine sulfate injection diluted in normal saline and lubricants
Authors: Wongwirawat Nuthida , Kuchonthara Nirachorn , Boontanomwong Sorrawit , Pongpirul Krit
Published: November 2022

Objective

As low-dose atropine eye-drops for myopia progression control prepared in-house by diluting the commercial 0.1% atropine eye-drop with sterile water or normal saline has been a common practice whereas atropine injection is readily available and could be a more feasible alternative, this study aimed to assess the properties of the in-house low-dose atropine eye-drops prepared by diluting the atropine injection in two solvents and tested in two temperature conditions.

Results

The 0.01% atropine eye-drops contains no bacteria, fungi, or particulate matter. The levels of atropine sulfate on all samples were comparable to the freshly prepared samples at the 12th week, regardless of the solvents used or storage conditions. The low-dose atropine eye-drops prepared from readily available atropine sulfate injection at healthcare facilities could be an alternative to commercial products.
Diagnosis of tuberculosis with autoimmune hepatitis–systemic lupus erythematosus overlap syndrome: a case report
Authors: Shekhar  , Gupta Nikita Yogesh , Harisingani Avi Ravi
Published: November 2022

Background

There is ample evidence indicating that immunosuppressive therapy or immune dysregulation in systemic lupus erythematosus increases the risk for tuberculosis. Interestingly, a few case reports suggest that tuberculosis could also be a risk factor for systemic lupus erythematosus and other autoimmune diseases.

Case presentation

We report the case of a 32-year-old Indian patient who was co-diagnosed with tuberculosis, systemic lupus erythematosus, and autoimmune hepatitis without any history of prior immunosuppression. This stresses the complex relationship between tuberculosis and autoimmune diseases.

Conclusion

Further research is warranted in this field to unfold the complex relationship between tuberculosis and systemic lupus erythematosus. It is essential to establish clear guidelines for the management of coexisting tuberculosis and systemic lupus erythematosus to promote individualized treatment.
Electroacupuncture as an effective therapy for Tapia’s syndrome after transoral intubation for general anesthesia: a case report and review of the literature
Authors: Xie Luan , Xiong Zhenyu , Xiao Weihong , Mo Yingnan , Li Xiangliang , Zhuang Xuan , Yang Ying , Jin Haipeng
Published: November 2022

Background

Tapia’s syndrome is a rare complication of airway manipulation under general anesthesia. Injuries to the vagus nerve (X) and hypoglossal nerve (XII) during transoral intubation are the primary cause of the disease. The typical symptoms include hoarseness, dysarthria, dysphagia, tongue muscle atrophy, and tongue deviation toward the affected side. We report a case of Tapia’s syndrome treated with electroacupuncture to accelerate the recovery process, and discuss the potential mechanism behind our findings based on previous research.

Case presentation

In this report, we describe a 57-year-old Chinese man who suffered Tapia’s syndrome after craniotomy evacuation of hematoma with general anesthesia and transoral intubation. After 52 days of electroacupuncture therapy along with standard swallowing training, the patient achieved significant improvement in deglutition and speech function.

Conclusion

Electroacupuncture is effective and safe for Tapia’s syndrome. It can shorten the recovery time when combined with routine swallowing rehabilitation.
ALDH2 gene polymorphism is associated with fitness in the elderly Japanese population
Authors: De Almeida Kathleen Yasmin , Saito Mika , Homma Hiroki , Mochizuki Yukina , Saito Aoto , Deguchi Minoru , Kozuma Ayumu , Okamoto Takanobu , Nakazato Koichi , Kikuchi Naoki
Published: November 2022

Purpose

The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which is exclusive to the Asian population, is related to many diseases. A high reactive oxygen species production in mitochondria, and low muscle strength in athletes and non-athletes, has been observed, as our previous study demonstrated. The purpose of this research was to investigate the influence of ALDH2 rs671 on the loss of muscle strength with aging and replicate our previous study in non-athletes.

Methods

Healthy Japanese individuals (n = 1804) aged 23–94 years were genotyped using DNA extracted from saliva. Muscle strength was assessed using grip strength and chair stand test (CST). The interaction between age and genotypes was analyzed by two-way analysis of covariance (ANCOVA) adjusted for sex, body mass index (BMI), and exercise habit.

Results

Individuals aged ≧55 with the AA genotype had a lower performance than those with the GG + GA genotype in the grip strength test (28.1 ± 9.1 kg vs. 29.1 ± 8.3 kg, p = 0.021). There was an interaction between age and genotype, where individuals with ≧55 years old AA genotype had a higher loss of strength compared to GG + GA genotypes in the CST (0.025). No interaction in other models and no sex differences were found.

Conclusion

This study replicated previous results of the relationship between the AA genotype with lower muscle strength and as a novelty showed that this genotype is associated with a higher age-related loss of strength.
A novel and dual digestive symbiosis scales up the nutrition and immune system of the holobiont Rimicaris exoculata
Authors: Aubé Johanne , Cambon-Bonavita Marie-Anne , Velo-Suárez Lourdes , Cueff-Gauchard Valérie , Lesongeur Françoise , Guéganton Marion , Durand Lucile , Reveillaud Julie
Published: November 2022

Background

In deep-sea hydrothermal vent areas, deprived of light, most animals rely on chemosynthetic symbionts for their nutrition. These symbionts may be located on their cuticle, inside modified organs, or in specialized cells. Nonetheless, many of these animals have an open and functional digestive tract. The vent shrimpRimicaris exoculatais fueled mainly by its gill chamber symbionts, but also has a complete digestive system with symbionts. These are found in the shrimp foregut and midgut, but their roles remain unknown. We used genome-resolved metagenomics on separate foregut and midgut samples, taken from specimens living at three contrasted sites along the Mid-Atlantic Ridge (TAG, Rainbow, and Snake Pit) to reveal their genetic potential.

Results

We reconstructed and studied 20 Metagenome-Assembled Genomes (MAGs), including novel lineages ofHepatoplasmataceaeandDeferribacteres, abundant in the shrimp foregut and midgut, respectively. Although the former showed streamlined reduced genomes capable of using mostly broken-down complex molecules,Deferribacteresshowed the ability to degrade complex polymers, synthesize vitamins, and encode numerous flagellar and chemotaxis genes for host-symbiont sensing. Both symbionts harbor a diverse set of immune system genes favoring holobiont defense. In addition,Deferribactereswere observed to particularly colonize the bacteria-free ectoperitrophic space, in direct contact with the host, elongating but not dividing despite possessing the complete genetic machinery necessary for this.

Conclusion

Overall, these data suggest that these digestive symbionts have key communication and defense roles, which contribute to the overall fitness of theRimicarisholobiont.
Viral community-wide auxiliary metabolic genes differ by lifestyles, habitats, and hosts
Authors: Luo Xiao-Qing , Wang Pandeng , Li Jia-Ling , Ahmad Manzoor , Duan Li , Yin Ling-Zi , Deng Qi-Qi , Fang Bao-Zhu , Li Shan-Hui , Li Wen-Jun
Published: November 2022

Background

Viral-encoded auxiliary metabolic genes (AMGs) are important toolkits for modulating their hosts’ metabolisms and the microbial-driven biogeochemical cycles. Although the functions of AMGs have been extensively reported in numerous environments, we still know little about the drivers that shape the viral community-wide AMG compositions in natural ecosystems. Exploring the drivers of viral community-wide AMG compositions is critical for a deeper understanding of the complex interplays among viruses, hosts, and the environments.

Results

Here, we investigated the impact of viral lifestyles (i.e., lytic and lysogenic), habitats (i.e., water, particle, and sediment), and prokaryotic hosts on viral AMG profiles by utilizing metagenomic and metatranscriptomic techniques. We found that viral lifestyles were the most important drivers, followed by habitats and host identities. Specifically, irrespective of what habitats viruses came from, lytic viruses exhibited greater AMG diversity and tended to encode AMGs for chaperone biosynthesis, signaling proteins, and lipid metabolism, which could boost progeny reproduction, whereas temperate viruses were apt to encode AMGs for host survivability. Moreover, the lytic and temperate viral communities tended to mediate the microbial-driven biogeochemical cycles, especially nitrogen metabolism, in different manners via AMGs. When focusing on each lifestyle, we further found clear dissimilarity in AMG compositions between water and sediment, as well the divergent AMGs encoded by viruses infecting different host orders.

Conclusions

Overall, our study provides a first systematic characterization of the drivers of viral community-wide AMG compositions and further expands our knowledge of the distinct interactions of lytic and temperate viruses with their prokaryotic hosts from an AMG perspective, which is critical for understanding virus-host-environment interactions in natural conditions.
Two cases of left ventricular apical aneurysm associated with severe aortic stenosis: case report
Authors: Koga Yuichi , Kamohara Keiji , Nogami Eijiro , Shimauchi Kouta , Takeuchi Yuki , Uchino Motonori , Morokuma Hiroyuki , Koga Shugo , Yunoki Junji
Published: November 2022

Background

Left ventricular (LV) apical aneurysm associated with aortic valve stenosis (AS) is very rare. We herein report two cases of this entity.

Case presentation

Case 1 was a 75-year-old woman admitted for surgery for severe AS and enlargement of the ascending aorta. Preoperative routine echocardiography and cardiac computed tomography (CT) revealed an unexpected local aneurysm of the LV apex. The patient underwent aortic valve replacement (AVR), LV aneurysm resection, and ascending aorta replacement. Case 2 was a 71-year-old woman diagnosed with severe AS. Preoperative cardiac CT detected LV apical aneurysm that could not be detected by echocardiography. Cardiac catheterization showed a coronary ventricular fistula. The patient underwent AVR and LV aneurysm resection. Given that neither of the two cases had a history of myocardial infarction or obstructive hypertrophic cardiomyopathy, the cause of the local aneurysm of the LV apex was thought to be relative ischemia at the apex due to myocardial hypertrophy and LV pressure overload due to long-term AS. In addition, a coronary artery fistula was suggested to be involved in the relative ischemia of the apex in Case 2.

Conclusions

Echocardiography alone is not sufficient to exclude apical aneurysm, and cardiac CT may be useful. Regarding the surgical indication, it is necessary to consider further cases in the future.