bluuebunny/crossref_metadata_2025_split huggingface dataset:
How does academia respond to the burden of infectious and parasitic disease?
Authors: Zhao Wenjing , Wang Lili , Zhang Lin 
Published: August 2022

Abstract
Background
Academic research is one of the main avenues through which humans can fight the threat of infectious diseases. However, there have been concerns regarding whether the academic system has provided sufficient efforts to fight infectious diseases we potentially face. Answering these questions could contribute to evidence-based recommendations for setting research priorities and third-mission policies.

Methods
With a focus on one of the most common categories of communicable diseases, infectious and parasitic diseases (IPDs), we searched Web of Science for articles and reviews relevant to IPDs published during the period 2000–2019 and retrieved WHO data on disease burden in corresponding years. The academic response patterns were explored by IPD subcategory and by human development level (an index established by the United Nations). We conduct the analysis in particular to gain insight into the dynamic relationship between disease burden and research effort on IPDs, scientific efforts contributed by countries with different development levels, and the variation trends in international joint efforts.

Results
The greatest burden of IPDs is clustered in the developing regions of Africa, but has received academic response from both developed and developing countries. Highly developed countries dominate the ranks of academic research in this area, yet there is also a clear increase in research efforts from the countries most affected, despite their low human development scale. In fact, the overall analysis reveals an improved capability for addressing local problems from African regions. In terms of international collaboration, highly developed countries such as the United States and United Kingdom have commonly collaborated with needy regions, whereas prolific but developing nations, like China, have not.

Conclusions
From a global perspective, academia has positively responded to health needs caused by IPDs. Although the relevant research output contribution is primarily from the highly developed countries, concentrated and specialized efforts from the undeveloped regions to ease their local burden can be clearly observed. Our findings also indicate a tendency to focus more on local health needs for both developed and undeveloped regions. The insights revealed in this study should benefit a more informed and systemic plan of research priorities.
Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus
Authors: Lee Wan-Fang , Fan Wen-Lang , Tseng Min-Hua , Yang Huang-Yu , Huang Jing-Long , Wu Chao-Yi 
Published: August 2022

Abstract
Background
Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5.

Case presentation
Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy.

Conclusions
Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.
A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature
Authors: Bryant Maria C. , Spencer L. Terry , Yalcindag Ali 
Published: August 2022

Abstract
Background
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare form of vasculitis in children. SARS-CoV-2, the virus that causes COVID-19 infection, seems to trigger autoimmunity and new-onset autoimmune disease in pediatric and adult patients. We present a case of new-onset AAV following COVID-19 infection in an adolescent patient, and we review the literature of AAV following COVID-19 infection.

Case presentation
An adolescent female with a history of asthma was diagnosed with mild COVID-19 infection and subsequently developed persistent cough, wheezing, hearing loss, arthralgias, and rash. Her imaging and laboratory workup showed pulmonary nodules and cavitary lesions, elevated inflammatory markers, negative infectious testing, and positive ANCA. She was treated with glucocorticoids, rituximab, and mycophenolate mofetil. At six-month follow-up, she had improvement in her symptoms, pulmonary function tests, imaging findings, and laboratory markers.

Conclusions
We report the second case of new-onset anti-PR3, C-ANCA vasculitis and the fourth case of pediatric-onset AAV following COVID-19 infection. A systematic review of the literature found 6 cases of new-onset AAV in adults after COVID-19 infection. Pediatric and adult patients who develop AAV post COVID-19 infection have few, if any, comorbidities, and show marked radiographic and symptomatic improvement after treatment. There is increasing evidence for COVID-19-induced autoimmunity in children and our case highlights the importance of considering AAV in a child following a recent COVID-19 infection because timely treatment may improve clinical outcomes.
Comparison of global indicators for severe maternal morbidity among South Korean women who delivered from 2003 to 2018: a population-based retrospective cohort study
Authors: Nam Jin Young 
Published: August 2022

AbstractBackgroundEven though several severe maternal morbidity (SMM) indicators exist globally, indicators that can serve as international standards are needed. Therefore, this study aimed to compare the SMM risk assessment using four international indicators and identify the factors underlying the differences among the risk assessments obtained by the various indicators.MethodsThis study used the National Health Insurance delivery cohort in South Korea from 2003 to 2018. SMM was estimated using four indicators: the United States Centers for Disease Control and Prevention (US-CDC) SMM algorithm, the American College of Obstetricians and Gynecologists (ACOG) gold standard guidelines, Zwart et al.’s indicators for the Netherlands, and the European Network on Severe Acute Maternal Morbidity (EURONET-SAMM) index. Generalized estimating equations models were used to identify the relationships between SMM indicators and risk factors.ResultsThe SMM incidence rates in 6,421,091 deliveries, were 2.36%, 3.12%, 0.31%, and 1.36% using the US-CDC, ACOG, Zwart et al.’s, and EURONET SAMM indicators, respectively. In sub indicators, hemorrhage-related codes constituted the highest proportion of all SMM indicators. Advanced maternal age was related to high risk in all four SMM indicators (US-CDC: 40–44 years, RR 1.67, 95% CI 1.63–1.71; ACOG’s guidelines: 40–44 years, RR 1.52, 95% CI 1.49–1.56; Zwart’s indicators: RR 2.72, 95% CI 2.55–2.90; EURONET-SAMM: RR 2.04, 95% CI 1.97–2.11) compared to those aged 25–29 years. In residential area, women who lived in rural area had approximately 1.2- to 1.5-fold higher risk of SMM compared to those who lived in Seoul. Additionally, inadequate prenatal care was associated with a 1.1- to 1.4-fold higher risk of SMM compared to adequate prenatal care.ConclusionsSMM was associated with maternal age, socioeconomic status, and adverse obstetric factors using various international SMM indicators. Further studies are needed to further determine risk and preventable factors for SMM and to identify more specific causes associated with the frequent sub-indicators of SMM.
Simultaneous versus staged bilateral total hip arthroplasty: a systematic review and meta-analysis
Authors: Ramezani Akam , Ghaseminejad Raeini Amirhossein , Sharafi Amirmohammad , Sheikhvatan Mehrdad , Mortazavi Seyed Mohammad Javad , Shafiei Seyyed Hossein 
Published: August 2022

Abstract
Background
Total hip arthroplasty is a common orthopedic surgery for treating primary or secondary hip osteoarthritis. Bilateral total hip replacement could be performed in a single stage or two separate stages. Each surgical procedure's reliability, safety, and complications have been reported controversially. This study aimed to review the current evidence regarding the outcomes of simultaneous and staged bilateral total hip arthroplasty.

Methods
We conducted a meta-analysis using MEDLINE, EMBASE, Web of Science, and Scopus databases. Eligible studies compared complications and related outcomes between simultaneous and staged bilateral THA. Two reviewers independently screened initial search results, assessed methodological quality, and extracted data. We used the Mantel–Haenszel method to perform the meta-analysis.

Results
In our study, we included 29,551 patients undergoing simBTHA and 74,600 patients undergoing stgBTHA. In favor of the simBTHA, a significant reduction in deep vein thrombosis (DVT) and systemic, local, and pulmonary complications was documented. However, we evidenced an increased pulmonary embolism (PE) and periprosthetic fracture risk in simBTHA. In the simBTHA, total blood loss, length of hospital stay, and total cost were lower.

Conclusion
This meta-analysis shows that simultaneous bilateral THA accompanies fewer complications and lower total cost. Well-designed randomized controlled trials are needed to provide robust evidence.
CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Authors: Zhang Xu , Guo Yeye , Xiao Ta , Li Jie , Guo Aiyuan , Lei Li , Jin Chong , Long Qi , Su Juan , Yin Mingzhu , Liu Hong , Chen Chao , Zhou Zhe , Zhu Susi , Tao Juan , Hu Shuo , Chen Xiang , Peng Cong 
Published: August 2022

Abstract
Background
Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear.

Methods
Epidermal CD147-overexpression or knockout (EpiCD147-OE or EpiCD147-KO) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation.

Results
We found that specific overexpression of CD147 in the epidermis (EpiCD147-OE) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in EpiCD147-OE transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in EpiCD147-OE transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of CD147D207-230. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs.

Conclusion
Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.
Revealing the crosstalk between nasopharyngeal carcinoma and immune cells in the tumor microenvironment
Authors: Jiang Jianyun , Ying Hongmei 
Published: August 2022

AbstractNasopharyngeal carcinoma (NPC) arises from the epithelial cells located in the nasopharynx and has a distinct geographic distribution. Chronic Epstein-Barr virus (EBV) infection, as its most common causative agents, can be detected in 100% of NPC types. In-depth studies of the cellular and molecular events leading to immunosuppression in NPC have revealed new therapeutic targets and diverse combinations that promise to benefit patients with highly refractory, advanced and metastatic NPC. This paper reviews the mechanisms by which NPC cells to circumvent immune surveillance and approaches being attempted to restore immunity. We integrate existing insights into anti-NPC immunity and molecular signaling pathways as well as targeting therapies in anticipation of broader applicability and effectiveness in advanced metastatic NPC.
The disruption of the CCDC6 – PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma
Authors: Morra Francesco , Merolla Francesco , Damia Giovanna , Ricci Francesca , Varricchio Silvia , Ilardi Gennaro , Arenare Laura , Califano Daniela , Napolitano Virginia , Fruscio Robert , Melillo Rosa Marina , Palazzo Luca , Celetti Angela 
Published: August 2022

AbstractBackgroundTreatment with PARP inhibitors (PARPi) is primarily effective against high-grade serous ovarian cancers (HGSOC) withBRCA1/2mutations or other deficiencies in homologous recombination (HR) repair mechanisms. However, resistance to PARPi frequently develops, mostly as a result ofBRCA1/2reversion mutations. The tumour suppressor CCDC6 is involved in HR repair by regulating the PP4c phosphatase activity on γH2AX. In this work, we reported that in ovarian cancer cells, a physical or functional loss of CCDC6 results synthetic lethal with the PARP-inhibitors drugs, by affecting the HR repair. We also unravelled a role for CCDC6 as predictive marker of PARPi sensitivity in ovarian cancer, and the impact of CCDC6 downregulation in overcoming PARPi resistance in these tumours.MethodsA panel of HGSOC cell lines (eitherBRCA-wild type or mutant) were treated with PARPi after CCDC6 was attenuated by silencing or by inhibiting USP7, a CCDC6-deubiquitinating enzyme, and the effects on cell survival were assessed. At the cellular and molecular levels, the processes underlying the CCDC6-dependent modification of drugs’ sensitivity were examined. Patient-derived xenografts (PDXs) were immunostained for CCDC6, and the expression of the protein was analysed statistically after digital or visual means.ResultsHGSOC cells acquired PARPi sensitivity after CCDC6 depletion. Notably, CCDC6 downregulation restored the PARPi sensitivity in newly generated or spontaneously resistant cells containing either wild type- or mutant-BRCA2. When in an un-phosphorylated state, the CCDC6 residue threonine 427 is crucial for effective CCDC6-PP4 complex formation and PP4 sequestration, which maintains high γH2AX levels and effective HR. Remarkably, the PP4-dependent control of HR repair is influenced by the CCDC6 constitutively phosphorylated mutant T427D or by the CCDC6 loss, favouring PARPi sensitivity. As a result, the PP4 regulatory component PP4R3α showed to be essential for both the activity of the PP4 complex and the CCDC6 dependent PARPi sensitivity. It's interesting to note that immunohistochemistry revealed an intense CCDC6 protein staining in olaparib-resistant HGSOC cells and PDXs.ConclusionsOur findings suggest that the physical loss or the functional impairment of CCDC6 enhances the PP4c complex activity, which causes BRCAness and PARPi sensitivity in HGSOC cells. Moreover, CCDC6 downregulation might overcome PARPi resistance in HGSOCs, thus supporting the potential of targeting CCDC6 by USP7 inhibitors to tackle PARPi resistance.
Evaluation of abdominal compression–decompression combined with chest compression CPR performed by a new device: Is the prognosis improved after this combination CPR technique?
Authors: Li Haishan , Wang Chao , Zhang Hongyuan , Cheng Fang , Zuo Shuang , Xu Liyou , Chen Hui , Wang Xiaodong 
Published: August 2022

AbstractIntroductionThis study was designed to compare the outcomes of standard cardiopulmonary resuscitation (STD-CPR) and combined chest compression and abdominal compression–decompression cardiopulmonary resuscitation (CO-CPR) with a new device following out-of-hospital cardiac arrest (OHCA). Moreover, we investigated whether patient prognosis improved with this combination treatment.MethodsThis trial was a single-centre, prospective, randomized trial, and a blinded assessment of the outcomes was performed. A total of 297 consecutive patients with OHCA were initially screened, and 278 were randomized to the STD-CPR group (n = 135) or the CO-CPR group (n = 143). We compared the proportions of patients who achieved a return of spontaneous circulation (ROSC), survived to hospital admission and survived to hospital discharge. In addition, we also performed the Kaplan–Meier analysis with a log-rank test at the end of the follow-up period to compare the survival curves of the two groups.ResultsThe differences were not statistically significant in the proportion of patients who achieved ROSC [31/135 (23.0%) versus 35/143 (24.5%)] and survived to hospital admission [28/135 (20.7%) versus 33/143 (23.1%)] between the CO-CPR group and STD-CPR group. However, there was a significant difference in the proportion of patients who survived to hospital discharge [16/135 (11.9%) versus 7/143 (4.9%)] between the two groups. Nine patients (6.7%) in the CO-CPR group and 2 patients (1.4%) in the STD group showed good neurological outcomes according to the cerebral performance category (CPC) scale score, and the difference was statistically significant (P = 0.003). The Kaplan–Meier curves showed that the patients in the CO-CPR group achieved better survival benefits than those in the STD-CPR group at the end of the follow-up period (log-rankP = 0.007).ConclusionCO-CPR was more beneficial than STD-CPR in terms of survival benefits in patients who have suffered out-of-hospital cardiac arrest.Trial registrationChinese Clinical Trial Registry, registered number:ChiCTR2100049581. Registered 30 July 2021- Retrospectively registered.http://www.medresman.org.cn/uc/index.aspx.
Open hemorrhoidectomy under local anesthesia versus saddle block in western Uganda: a study protocol for a prospective equivalence randomized, double-blind controlled trial
Authors: Sikakulya Franck Katembo , Ssebuufu Robinson , Okedi Xaviour Francis , Baluku Moris , Lule Herman , Kyamanywa Patrick 
Published: August 2022

Abstract
Background
While open hemorrhoidectomy under local anesthesia has been shown to be more cost-effective with shorter operation times and lower complication rates, local anesthesia is still not considered as a first-line technique in low-income countries like Uganda. The objective of this trial is to compare open hemorrhoidectomy using local anesthesia versus saddle block among patients with primary uncomplicated 3rd- or 4th-degree hemorrhoids in western Uganda.

Methods
The protocol for a prospective equivalence randomized, double-blind controlled trial was conducted among patients with primary uncomplicated 3rd- or 4th-degree hemorrhoids. Recruitment was started in December 2021 and is expected to end in May 2022. Consenting participants who require open hemorrhoidectomy indicated at Kampala International Teaching Hospital, Uganda, will be randomized into two groups of 29 patients per arm.

Discussion
The primary outcome of this study is to compare the occurrences of postoperative pain following open hemorrhoidectomy using the visual analog scale in an interval of 2, 4, and 6 h and 7 days postoperatively. Furthermore, the mean operative time from the induction of anesthesia to the end of the surgical procedure as well as the cost-effectiveness of the 2 techniques will be assessed in both groups. Open hemorrhoidectomy under local anesthesia has the potential to offer benefits to patients but most importantly expediting return to baseline and functional status, shorter hospital stay by meeting the faster discharge criteria, and reduction in costs associated with reduced length of stay and complications.

Trial registration
Pan African Clinical Trials Registry PACTR202110667430356. Registered on 8 October 2021
Abatacept downregulates Fcγ receptor I on circulating monocytes: a potential therapeutic mechanism in patients with rheumatoid arthritis
Authors: Fukue Ryosuke , Okazaki Yuka , Gono Takahisa , Kuwana Masataka 
Published: August 2022

Abstract
Background
Abatacept is a recombinant fusion protein composed of the extracellular domain of cytotoxic T-lymphocyte antigen 4 and the Fc portion of immunoglobulin (Ig) G. The mechanism of action of abatacept in rheumatoid arthritis (RA) is believed to be competitive inhibition of T cell costimulation mediated by the binding of CD28 to CD80/CD86 on antigen-presenting cells, and recent studies have shown that abatacept induces reverse signaling in macrophages and osteoclast precursors in a T cell-independent manner. This study aimed to investigate the therapeutic effects of abatacept on circulating monocytes that contribute to RA pathogenesis.

Methods
Purified circulating monocytes derived from RA patients and controls were cultured in the absence or presence of abatacept or CD28-Ig for 24 h. The recovered cells were subjected to flow cytometry to evaluate the expression levels of cell surface molecules, and cytokines and chemokines in the culture supernatant were measured by multiplex bead arrays. The expression of candidate molecules was further examined by immunoblotting using total cellular extracts of the cultured monocytes. Finally, the effects of abatacept on cytokine production in monocytes stimulated with the immune complex of anti-citrullinated peptide antibodies (ACPAs) were examined.

Results
CD64/FcγRI was identified as a monocyte-derived molecule that was downregulated by abatacept but not CD28-Ig. This effect was observed in both RA patients and controls. The abatacept-induced downregulation of CD64/FcγRI was abolished by treatment with anti-CD86 antibodies but not anti-CD80 antibodies. Abatacept suppressed the production of interleukin (IL)-1β, IL-6, C-C motif chemokine ligand 2, and tumor necrosis factor-α in cultured monocytes stimulated with the ACPA immune complex.

Conclusions
The therapeutic effects of abatacept on RA are mediated, in part, by the downregulation of CD64/FcγRI on circulating monocytes via direct binding to CD86 and the suppression of immune complex-mediated inflammatory cytokine production.