bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsideration of Return-to-Sport Decision-Making After Pediatric ACL Injury: A Scoping Review
Authors: Pauw Anne Hendrika Johanna , Buck Tristan Marcel Frank , Gokeler Alli , Tak Igor Joeri Ramon
Published: January 2023

Context:

Up to 90% of pediatric athletes return to sport (RTS) after anterior cruciate ligament reconstruction (ACL-R); however, <50% RTS at the same level and second ACL injury rates are up to 32%.

Objectives:

(1) Determine which physical and patient-reported outcome measures guide clinical decision-making on RTS in pediatric athletes after ACL-R and (2) present a framework with insights from cognitive and neurophysiological domains to enhance rehabilitation outcomes.

Data Sources:

PubMed, CINAHL, Embrase, and Cochrane library databases and gray literature.

Study Selection:

Data on pediatric (<18 years) ACL-R patients, RTS, tests, and decision-making were reported in 1214 studies. Two authors independently reviewed titles and abstract, excluding 962 studies. Gray literature and cross-reference checking resulted in 7 extra studies for full-text screening of 259 studies. Final data extraction was from 63 eligible studies.

Study Design:

Scoping review.

Level of Evidence:

Level 4.

Data Extraction:

Details on study population, aims, methodology, intervention, outcome measures, and important results were collected in a data chart.

Results:

Studies included 4456 patients (mean age, 14 years). Quadriceps and hamstring strength (n = 25), knee ligament arthrometer (n = 24), and hop tests (n = 22) were the most-reported physical outcome measures guiding RTS in <30% of studies with cutoff scores of limb symmetry index (LSI) ≥85% or arthrometer difference <3 mm. There were 19 different patient-reported outcome measures, most often reporting the International Knee Documentation Committee (IKDC) (n = 24), Lysholm (n = 23), and Tegner (n = 15) scales. Only for the IKDC was a cutoff value of 85% reported.

Conclusion:

RTS clearance in pediatric ACL-R patients is not based on clear criteria. If RTS tests were performed, outcomes did not influence time of RTS. Postoperative LSI thresholds likely overestimate knee function since biomechanics are impaired despite achieving RTS criteria. RTS should be considered a continuum, and biomechanical parameters and contextual rehab should be pursued with attention to the individual, task, and environment. There is a need for psychological monitoring of the ACL-R pediatric population.
Clinical and epidemiological features of paroxysmal cold hemoglobinuria: a systematic review
Authors: Jacobs Jeremy W. , Figueroa Villalba Cristina A. , Booth Garrett S. , Woo Jennifer S. , Stephens Laura D. , Adkins Brian D.
Published: January 2023

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis and is challenging to diagnose because of the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL and nadir of 5.5 g/dL. The most common direct antiglobulin test (DAT) result was the presence of complement and absence of immunoglobulin G (IgG) bound to red blood cells, although other findings were observed in one-third of cases. DL antibody class and specificity were reported for 71 patients, of which 83.1% were IgG anti-P. The use of corticosteroids is common, although we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Among patients with follow-up, 99% (213 of 216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered that contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.
Human liver microbiota modeling strategy at the early onset of fibrosis
Authors: Champion Camille , Neagoe Radu M. , Effernberger Maria , Sala Daniela T. , Servant Florence , Christensen Jeffrey E. , Arnoriaga-Rodriguez Maria , Amar Jacques , Lelouvier Benjamin , Loubieres Pascale , Azalbert Vincent , Minty Matthieu , Thomas Charlotte , Blasco-Baque Vincent , Gamboa Fabrice , Tilg Herbert , Cardellini Marina , Federici Massimo , Fernández-Real Jose-Manuel , Loubes Jean Michel , Burcelin Rémy
Published: January 2023

Background

Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences.

Results

Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0.

Conclusions

Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.

Trial registration

TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.
Superior mesenteric artery embolism after radiofrequency ablation in regularly anticoagulated patients with paroxysmal atrial fibrillation: a case report
Authors: Jing Yongle , Xu Jianqiang , Chen Bingwei , Xia Dasheng , Xia Dachuan , Tian Yunpeng , Xia Wei , Lu Chengzhi , Wu Yuli
Published: January 2023

Background

Superior mesenteric artery embolism (SMAE) is a rare cause of acute abdomen, and the fatality rate is extremely high if it is not diagnosed and treated in time. Due to the lack of knowledge and experience of nonspecialist physicians, it is easy to misdiagnose. Radiofrequency ablation (RFA) has become the first-line treatment strategy for atrial fibrillation (AF). Thromboembolic events are some of the major complications after RFA, whereas SMAE is rarely reported.

Case presentation

A 70 year-old woman with paroxysmal AF who regularly took anticoagulant drugs for 3 months experienced abdominal pain after RFA. At the outset, she was misdiagnosed as mechanical intestinal obstruction. When the patient presented with blood in the stool, abdominal enhancement computed tomography was conducted and showed a small bowel perforation. Immediate laparotomy was performed, and the final diagnosis was SMAE.

Conclusion

It is suggested that for unexplained abdominal pain after RFA of AF, the possibility of SMAE should be considered, and a targeted examination should be carried out in time to confirm the diagnosis and give appropriate treatment.
No advantage of single day 6 good-quality blastocyst transfer versus single day 5 poor-quality blastocyst transfer in frozen-thawed cycles stratified by age: a retrospective study
Authors: He Yuxia , Tang Yan , Liu Haiying , Liu Jianqiao , Mao Yuling
Published: January 2023

Background

Blastocyst developmental speed, morphological grading and patient age are associated with pregnancy outcomes of frozen-thawed cycles. This study aimed to compare the clinical and neonatal outcomes between poor-quality D5 blastocysts and good-quality D6 blastocysts stratified by patient age.

Methods

A total of 1,623 cycles were divided into two groups: group A (n = 723) received one D5 poor-quality blastocyst; group B (n = 900) received one D6 good-quality blastocyst. Pregnancy and neonatal outcomes were compared among the four groups stratified by 35 years of age.

Results

When patients were in the same age group, there was no significant difference in terms of age, body mass index, infertility duration, infertility type, fertilization method, proportion of endometrial preparation protocols, and endometrial thickness between D5 poor-quality and D6 high-quality blastocysts groups. Live birth rate of D5 poor-quality blastocysts was higher than that of D6 high-quality blastocysts for patients aged < 35 years (35.48% vs. 31.13%, p > 0.05), but there was no statistical difference. The same trend was showed for patients aged ≥ 35 years (29.09% vs. 21.28%, p > 0.05). Moreover, when patients were in the same age category, there was no significant difference in terms of gestational age, birth weight, birth height, and rates of preterm birth, low birth weight, and very low birth weight between groups A and B.

Conclusions

The preferential selection of poor-quality D5 blastocysts for transfer compared to high-quality D6 blastocysts is recommended, especially for advanced age patients. Single good-quality D6 blastocyst transfer can be considered for the acceptable live birth rate.
Combined anti-C1-INH and radiotherapy against glioblastoma
Authors: Liljedahl Emma , Konradsson Elise , Gustafsson Emma , Jonsson Karolina Förnvik , Olofsson Jill K. , Osther Kurt , Ceberg Crister , Redebrandt Henrietta Nittby
Published: January 2023

Background

A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting.

Methods

Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately.

Results

In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals.

Conclusions

Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.
Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England
Authors: Mohanty Salini , Podmore Bélène , Cuñado Moral Ana , Weiss Thomas , Matthews Ian , Sarpong Eric , Méndez Ignacio , Qizilbash Nawab
Published: January 2023

Background

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children.

The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs).

Methods

AOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models.

Results

From 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2–4 years: 7951.8 (95% CI 7902.5-8001.4); 5–17 years: 2184.4 (95% CI 2172.1–2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85–0.89), early post-PCV13 0.88 (95% CI 0.86–0.91), and late post-PCV13 0.75 (95% CI 0.73–0.78).

Conclusions

The AOM IRs declined during the 2003–2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.
Development of a prognostic nomogram for sepsis associated-acute respiratory failure patients on 30-day mortality in intensive care units: a retrospective cohort study
Authors: Luo Mengdi , He Qing
Published: January 2023

Background

Acute respiratory failure is a type of sepsis complicated by severe organ failure. We have developed a new nomogram for predicting the 30-day risk of death in patients through a retrospective study.

Method

Data was collected and extracted from MIMICIV, with 768 eligible cases randomly assigned to the primary cohort (540) and the validation cohort (228). The final six factors were included by Cox regression analysis to create the Nomogram, the accuracy of the Nomogram was assessed using the C-index and calibration curve, and finally, the clinical usefulness of the Nomogram was evaluated using DCA in.

Results

Multivariate Cox regression analysis showed that age, DBP, lactate, PaO2, platelet, mechanical ventilation were independent factors for 30-day mortality of SA-ARF. The nomogram established based on the six factors. The C-index of nomogram in the primary cohort is 0.731 (95% CI 0.657–0.724) and 0.722 (95%CI 0.622–0.759) in the validation cohort. Besides, the decision curve analysis (DCA) confirmed the clinical usefulness of the nomogram.

Conclusion

The study developed and validated a risk prediction model for SA-ARF patients that can help clinicians reasonably determine disease risk and further confirm its clinical utility using internal validation.
Magnitude of undernutrition and associated factors among adult tuberculosis patients attending public health facilities in Haramaya District, Eastern Ethiopia
Authors: Tadesse Fasika , Mitiku Habtamu , Girma Sagni , Kenay Abera
Published: January 2023

Background

Tuberculosis is one of the top ten causes of illness, death, and disability throughout the world. Undernutrition reduces immunity, which makes latent tuberculosis more likely to become active tuberculosis. Tuberculosis makes these conditions worse. The body of a person suffering from TB has an increased demand for energy, which often causes a TB patient to lose a significant amount of weight and this can worsen acute undernutrition. The aim of this study was to assess the magnitude of undernutrition and its associated factors among adult TB patients in public health facilities in Haramaya district, eastern Ethiopia.

Methods

Institution-based cross-sectional study was conducted among 330 adult tuberculosis patients on follow-up in public health facility of Haramaya District, eastern Ethiopia from January 10, 2021 to February 20, 2021. An anthropometric assessment was done after a face-to-face interview using a pretested structured questionnaire. SPSS 24 was used to analyze the data. Bivariable and multivariable logistic regression model was used to identify factors associated with undernutrition.

Results

The overall prevalence of undernutrition was 43.6% (95% CI 38.2–49.1%). Proportion of severe, moderate and mild undernutrition was 11.8%, 12.4%, and 19.4%, respectively. Age group of 18–24 years (AOR = 4.12; 95% CI 1.36–12.51), not have formal education (AOR = 1.76; 95% CI 1.01–3.08), having large family size (AOR = 2.62; 95% CI 1.43–4.82), low dietary diversity (AOR = 2.96; 95% CI 1.75–4.99), lack of latrine (AOR = 2.14; 95% CI 1.26–3.65), history of TB treatment (AOR = 2.56; 95% CI 1.19–5.54) and taking intensive phase of anti-TB drugs (AOR = 3.18; 95% CI 1.62–6.25) were factors found significantly associated with under nutrition.

Conclusion

The prevalence of undernutrition was high. Age, educational status, family size, dietary diversity, toilet facility, history of tuberculosis medication and intensive phase of anti-TB drugs were found significantly associated with undernutrition. The nutritional derangement could call for fast nutritional intervention in the management of pulmonary tuberculosis patients.
Development and validation of a nomogram for survival prediction in hepatocellular carcinoma after partial hepatectomy
Authors: Lu Yang , Ren Shuang , Jiang Jianning
Published: January 2023

Background

The prognosis for hepatocellular carcinoma (HCC) is complex due to its high level of heterogeneity, even after radical resection. This study was designed to develop and validate a prognostic nomogram for predicting the postoperative prognosis for HCC patients following partial hepatectomy.

Patients and methods

We extracted data on HCC patients and randomly divided them into two groups (primary and validation cohorts), using the Surveillance, Epidemiology and End Results (SEER) database. We developed the prediction model based on the data of the primary cohort and prognostic factors were evaluated using univariate and multivariate Cox regression analysis. A nomogram was constructed for predicting the 1-, 3-, and 5-year survival probability of HCC patients after surgery based on the results of the multivariate Cox regression analysis. The performance of the nomogram was evaluated in terms of its discrimination and calibration. To validated the model, discrimination and calibration were also evaluated in the validation cohort. Decision curve analysis (DCA) was performed to assess the clinical utility of the nomogram.

Results

A total of 890 patients who underwent partial hepatectomy for HCC were included in the study. The primary cohort enrolled 628 patients with a median follow-up time of 39 months, the 1-, 3-, and 5-year survival rate were 95.4%, 52.7% and 25.8% during follow-up. Multivariate Cox regression analysis showed that differentiation, tumor size, AFP and fibrosis were independently association with the prognosis of HCC patients after partial hepatectomy. The nomogram showed a moderate discrimination ith a C-index of 0.705 (95% CI 0.669 to 0.742), and good calibration. Similar discrimination with a C-index of 0.681 (95% CI 0.625 to 0.737), and calibration were also observed in the validation cohort. Decision curve analysis showed that the nomogram could be useful to predicting the prognosis in HCC patients following partial hepatectomy.

Conclusions

The proposed nomogram is highly predictive and has moderate calibration and discrimination, potentially contributing to the process of managing HCC patients after partial hepatectomy in an individualized way.
Perceptions of medical students towards the role of histology and embryology during curricular review
Authors: Carneiro Bruno Daniel , Pozza Daniel Humberto , Tavares Isaura
Published: January 2023

Background

The continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology.

Methods

Medical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum.

Results

Four hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes.

Conclusions

Our study contributes to the debate about the evolution of medical curriculum. Gathering the medical students’ perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.
Detection and description of a novel Psychrobacter glacincola infection in some Red Sea marine fishes in Hurghada, Egypt
Authors: El-Sayed Mohamed Raafat , Emam Arafah M. , Osman Ahmed Elsayed , Abd El-Galil Mohamed Abd El-Aziz Ahmed , Sayed Haitham Helmy
Published: January 2023

An important food-producing sector in Egypt is aquaculture and fisheries; however, several pathogenic microorganisms lead to high mortalities and significant economic losses. The occurrence ofPsychrobacter glacincolainfection among 180 wild marine fishes collected from the Red sea at Hurghada, Egypt were investigated in the present study. The disease prevalence rate was 6.7%. The recovered isolates were subjected to biochemical and molecular identification. The study also investigated pathogenicity and the antibiogram profile of the recovered isolates. The clinical examination of the infected fish revealed various signs that included lethargy and sluggish movement, hemorrhages and ulcers on the body and the operculum, scale loss, and fin congestion and rot, especially at the tail fin. Furthermore, during postmortem examination, congestion of the liver, spleen, and kidney was observed. Interestingly, 12 isolates were recovered and were homogenous bacteriologically and biochemically. The phylogenetic analysis based on 16S rRNA gene confirmed that MRB62 identified strain was closely related the genus Psychrobacter and identified asP. glacincolaand was pathogenic toRhabdosargus haffarafish, causing 23.3% mortality combined with reporting a series of clinical signs similar to that found in naturally infected fishes. The present study also showed thatP. glacincolaisolates were sensitive to all antibiotics used for sensitivity testing. Our findings add to the body of knowledge regarding the occurrence of pathogenicP. glacincolainfection in Egyptian marine fishes and its potential effects on fish. Future large-scale surveys exploring this bacterium among other freshwater and marine fishes in Egypt would be helpful for the implementation of effective strategies for the prevention and control of this infection are warranted.
Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model
Authors: Xu Yinlan , Wan Shuangxiu , Sun Panpan , Khan Ajab , Guo Jianhua , Zheng Xiaozhong , Sun Yaogui , Fan Kuohai , Yin Wei , Li Hongquan , Sun Na
Published: January 2023

Background

Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days.

Results

The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.

Conclusions

The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.
Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis
Authors: Ekmejian Avedis , Sritharan Hari , Selvakumar Dinesh , Venkateshka Venkateshka , Allahwala Usaid , Ward Michael , Bhindi Ravinay
Published: January 2023

Background

Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of  > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR.

Methods

We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR  > 0.8 were included. The primary end point was MACE.

Results

The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35–2.04, p =  < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06–2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20–2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07–4.05, p = 0.03).

Conclusions

For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients.

Trail registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022367312.
CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances
Authors: Maalej Karama Makni , Merhi Maysaloun , Inchakalody Varghese P. , Mestiri Sarra , Alam Majid , Maccalli Cristina , Cherif Honar , Uddin Shahab , Steinhoff Martin , Marincola Francesco M. , Dermime Said
Published: January 2023

In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.
Stop GnRH-agonist/GnRH-antagonist protocol: a different insight on ovarian stimulation for IVF
Authors: Orvieto Raoul
Published: January 2023

Ovarian stimulation (OS) is one of the key factors in the success of in vitro fertilization-embryo transfer (IVF-ET), by enabling the recruitment of numerous healthy fertilizable oocytes and, thereby, multiple embryos. The Stop GnRH-agonist/GnRH-antagonist (GnRH-ag/GnRH-ant), which offers all the advantages of using long suppressive GnRH-ag, with GnRH-ant, is in my opinion a valuable addition to the armamentarium of OS protocols. It allows cycle programming, better follicular synchronization and offers successful outcome in a variety of challenging cases such as poor responders, Poseidon group 4 poor prognosis patients, those with elevated peak progesterone (P) serum levels, poor embryo quality or repeated IVF failures.
Mechanical performance of porous biomimetic intervertebral body fusion devices: an in vitro biomechanical study
Authors: Tsuang Fon-Yih , Li Ming-Jun , Chu Po-Han , Tsou Nien-Ti , Sun Jui-Sheng
Published: January 2023

Background

Degenerative disc disease is one of the most common ailments severely affecting the quality of life in elderly population. Cervical intervertebral body fusion devices are utilized to provide stability after surgical intervention for cervical pathology. In this study, we design a biomimetic porous spinal cage, and perform mechanical simulations to study its performances following American Society for Testing and Materials International (ASTM) standards before manufacturing to improve design process and decrease cost and consumption of material.

Methods

The biomimetic porous Ti-6Al-4 V interbody fusion devices were manufactured by selective laser melting (laser powder bed fusion: LPBF in ISO/ASTM 52900 standard) and subsequently post-processed by using hot isostatic pressing (HIP). Chemical composition, microstructure and the surface morphology were studied. Finite element analysis and in vitro biomechanical test were performed.

Findings

The post heat treatment can optimize its mechanical properties, as the stiffness of the cage decreases to reduce the stress shielding effect between two instrumented bodies. After the HIP treatment, the ductility and the fatigue performance are substantially improved. The use of HIP post-processing can be a necessity to improve the physical properties of customized additive manufacturing processed implants.

Interpretation

In conclusion, we have successfully designed a biomimetic porous intervertebral device. HIP post-treatment can improve the bulk material properties, optimize the device with reduced stiffness, decreased stress shielding effect, while still provide appropriate space for bone growth.

Clinical significance

The biomechanical performance of 3-D printed biomimetic porous intervertebral device can be optimized. The ductility and the fatigue performance were substantially improved, the simultaneously decreased stiffness reduces the stress shielding effect between two instrumented bodies; while the biomimetic porous structures provide appropriate space for bone growth, which is important in the patients with osteoporosis.
Germline-related molecular phenotype in Metazoa: conservation and innovation highlighted by comparative transcriptomics
Authors: Piccinini Giovanni , Milani Liliana
Published: January 2023

Background

In Metazoa, the germline represents the cell lineage devoted to the transmission of genetic heredity across generations. Its functions intuitively evoke the crucial roles that it plays in organism development and species evolution, and its establishment is tightly tied to animal multicellularity itself. The molecular toolkit expressed in germ cells has a high degree of conservation between species, and it also shares many components with the molecular phenotype of some animal totipotent cell lineages, like planarian neoblasts and sponge archaeocytes. The present study stems from these observations and represents a transcriptome-wide comparative analysis between germline-related samples of 9 animal species (7 phyla), comprehending also totipotent lineages classically considered somatic.

Results

Differential expression analyses were performed for each species between germline-related and control somatic tissues. We then compared the different germline-related transcriptional profiles across the species without the need for an a priori set of genes. Through a phylostratigraphic analysis, we observed that the proportion of phylum- and Metazoa-specific genes among germline-related upregulated transcripts was lower than expected by chance for almost all species. Moreover, homologous genes related to proper DNA replication resulted the most common when comparing the considered species, while the regulation of transcription and post-transcriptional mechanisms appeared more variable, showing shared upregulated functions and domains, but very few homologous whole-length sequences.

Conclusions

Our wide-scale comparative analysis mostly confirmed previous molecular characterizations of specific germline-related lineages. Additionally, we observed a consistent signal throughout the whole data set, therefore comprehending both canonically defined germline samples (germ cells), and totipotent cell lineages classically considered somatic (neoblasts and archaeocytes). The phylostratigraphic analysis supported the less probable involvement of novel molecular factors in the germline-related transcriptional phenotype and highlighted the early origin of such cell programming and its conservation throughout evolution. Moreover, the fact that the mostly shared molecular factors were involved in DNA replication and repair suggests how fidelity in genetic material inheritance is a strong and conserved driver of germline-related molecular phenotype, while transcriptional and post-transcriptional regulations appear differently tuned among the lineages.
Psychiatric sequelae of thromboangiitis obliterans: a case report and review of the literature
Authors: Awara Mahmoud A. , Downing Laura M. , Elnenaei Manal O.
Published: January 2023

Background

Peripheral manifestations secondary to progressive vascular occlusions are characteristic of the rare condition termed thromboangiitis obliternas (TAO) or Buerger’s disease. The central manifestations of this disease are however poorly characterized, particularly those of psychiatric nature, and their prevalence is largely unknown. Speculations have been made around the polymorphic nature and triggers of observed psychopathology in TAO; much however remains to be unraveled in this area.

Case presentation

We present the case of a 33-year-old Caucasian male who developed first episode of psychosis at the age of 29 years. There was no history of previous mental illness either in the patient, or in any of his family members. He had been a long- term heavy smoker and was experiencing progressive lower limb claudication since the age of 22 years; however, all inflammatory, autoimmune and atherosclerotic markers were negative. His psychosis was characterized by retention of a warm affect, and despite some amelioration, was generally resistant to a fair trial of several anti-psychotic medications including Clozapine.

Conclusion

The pathophysiology of psychosis secondary to Buerger’s is not yet well characterized which adds to the complexity of managing these cases. Recognizing that cerebral manifestations of this disease may evolve several years after the onset of peripheral thromboangiitic features is important for following the natural history and considering measures that may reduce the burden of illness.
Severe skin and soft tissue infection in the left upper limb caused by Aeromonas veronii: a case report
Authors: Li Linhui , Huang Jie , Xu Long , Wang Guangyi , Xiao Shichu , Xia Zhaofan , Qin Qin , Li Yazhou , Ji Shizhao
Published: January 2023

Introduction

Skin and soft tissue infections are common because of exposure to aquatic environment, while severe infections caused by Aeromonas veronii are rare.

Case presentation

We report a case of severe skin and soft tissue infection of the left upper limb caused by Aeromonas veronii. A 50-year-old Chinese woman, who had a history of cardiac disease and type 2 diabetes mellitus, accidentally injured her left thumb while cutting a fish. Early antibiotic therapy and surgical debridement was performed before the result of bacterial culture came back. Whole-genome sequencing was further performed to confirm the pathogen and reveal the drug resistance and virulence genes. The wound was gradually repaired after 1 month of treatment, and the left hand recovered well in appearance and function after 3 months of rehabilitation.

Conclusion

Early diagnosis, surgical intervention, and administration of appropriate antibiotics are crucial for patients who are suspected of having skin and soft tissue infection, or septicemia caused by Aeromonas veronii.
Analysis of clinical features and risk factors of peripheral neuropathy in patients with primary Sjögren's syndrome
Authors: Wu Zhihong , Wang Dong , Chen Lirong , Xianyu Kaipu , Yang Huiqing
Published: January 2023

Objective

To observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS.

Methods

Sixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy.

Results

The patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased.

Conclusion

PN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.
Radiosynthesis and preclinical evaluation of [11C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging
Authors: Cools Romy , Vermeulen Koen , Narykina Valeria , Leitao Renan C. F. , Bormans Guy
Published: January 2023

Background

The molecular chaperone, Hsp90, is a key player in the protein quality control system that maintains homeostasis under cellular stress conditions. It is a homodimer with ATP-dependent activity, and is a prominent member of the chaperone machinery that stabilizes, matures and (re)folds an extensive list of client proteins. Hsp90 occurs as four isoforms, cytosolic Hsp90α and Hsp90β, mitochondrial TRAP1 and Grp94 present in the endoplasmic reticulum. An aberrant role of Hsp90 has been attributed to several cancers and neurodegenerative disorders. Consequently, Hsp90 has emerged as an attractive therapeutic target. However, pan-Hsp90 inhibition often leads to detrimental dose-limiting toxicities. Novel strategies for Hsp90-targeted therapy intend to avoid this by using isoform-specific Hsp90 inhibition. In this respect, the radiosynthesis of carbon-11 labeled SNX-ab was developed and [11C]SNX-ab was evaluated as a Hsp90α,β isoform-selective PET probe, which could potentially allow to quantify in vivo Hsp90α,β expression.

Results

[11C]SNX-ab was synthesized with excellent radiochemical yields of 45% and high radiochemical purity (> 98%). In vitro autoradiography studies on tissue slices of healthy mouse brain, mouse B16.F10 melanoma and U87 glioblastoma using homologous (SNX-ab, SNX-0723) and heterologous (Onalespib and PU-H71) Hsp90 inhibitors demonstrated only limited reduction of tracer binding, indicating that the binding of [11C]SNX-ab was not fully Hsp90-specific. Similarly, [11C]SNX-ab binding to U87 cells was not efficiently inhibited by Hsp90 inhibitors. Ex vivo biodistribution studies in healthy mice revealed limited brain exposure of [11C]SNX-ab and predominantly hepatobiliary clearance, which was confirmed by in vivo full-body dynamic µPET studies.

Conclusion

Our results suggest that [11C]SNX-ab is not an ideal probe for in vivo visualization and quantification of Hsp90α/β expression levels in tumour and brain. Future research in the development of next-generation Hsp90 isoform-selective PET tracers is warranted to dissect the role played by each isoform towards disease pathology and support the development of subtype-specific Hsp90 therapeutics.
Mapping and gap analysis on antimicrobial resistance surveillance systems in Kenya, Tanzania, Uganda and Zambia
Authors: Matee Mecky , Mshana Stephen E. , Mtebe Majigo , Komba Erick Vitus , Moremi Nyambura , Lutamwa Julius , Kapona Otrida , Sekamatte Musa , Mboera Leonard E. G.
Published: January 2023

Background

Antimicrobial resistance is a global problem and involve pathogens which have the potential to move between food producing animals and humans by direct exposure or through the food chain or the environment. The objective of this study was to determine the performance in addressing antimicrobial resistance in Kenya, Tanzania, Uganda and Zambia. Desk review and in-depth interviews were employed for data collection. Interviews were conducted with national antimicrobial resistance focal officials.

Results

The findings indicate that in the four countries there was minimal capacity to conduct AMR surveillance. There were few well-established laboratories in tertiary hospitals, both private and public hospitals. The animal, environment and agricultural sectors in all countries had limited capacity in conducting antimicrobial resistance surveillance. There is limited data on antimicrobial resistance in all the four countries, and regional data sharing was limited. In all the four countries, data from research institutions were not linked using standardized system making difficult to compile the national database. The capacity for microbiological culture, identification and antimicrobial sensitivity testing using standardized protocols was available in the four countries. The interventions adopted by the countries included development of National Action Plans on antimicrobial resistance and setting up of multi-sectoral national coordinating structures.

Conclusions

Based on this findings, the countries need improved National Integrated Antimicrobial Resistance Surveillance systems to include community settings, involving antimicrobial use and resistance in human, animal, food, and environment sectors. In addition, the region requires clear antimicrobial resistance data sharing protocol for quick comparability of the data across the region. This is important in driving antimicrobial resistance agendas at regional level, which will eventually trigger collective actions.