bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 4-hexylresorcinol administration on the submandibular glands in a growing rat model
Authors: Yoon Joo-Hyung , Kim Dae-Won , Lee Suk Keun , Kim Seong-Gon 
Published: June 2022

Abstract
Background
4-Hexylresorcinol (4HR) is a food additive and class I histone deacetylase inhibitor. In this study, we examined the effects of 4HR administration on the submandibular gland in a growing rat model.

Methods
Four-week-old rats were used in this study. The experimental group (nine males and eight females) received 12.8 mg/kg of 4HR weekly for 12 weeks. Ten rats (five males and five females) were used as controls. The submandibular glands of rats were collected 12 weeks after the first administration of 4HR. The weight of the glands was measured. Histological analysis, immunoprecipitation-high-performance liquid chromatography (IP-HPLC), and western blotting were performed.

Results
The weights of the rat submandibular glands were higher in the experimental groups than in the control group, especially in male rats (P < 0.05). The vascular endothelial growth factor (VEGF) and testosterone in the submandibular glands were more highly expressed in 4HR-treated male rats than in untreated rats, as detected by both western blotting and immunohistochemistry. The IP-HPLC results demonstrated that the expression levels of Ki67, epidermal growth factor, and testosterone in the submandibular glands were higher in 4HR-treated male rats than in untreated rats.

Conclusions
This study demonstrated that the systemic administration of 4HR increased the weight of submandibular glands in male rats. In addition, the testosterone and VEGF expression levels in the submandibular glands increased owing to 4HR administration.
Concomitant septic arthritis of the hip joint and femoral head avascular necrosis in patients with recent COVID-19 infection: a cautionary report
Authors: Ardakani Mohammad Vahedian , Parviz Sara , Ghadimi Ehsan , Zamani Zahra , Salehi Mohammadreza , Firoozabadi Mohammad Ayati , Mortazavi S. M. Javad 
Published: June 2022

Abstract
Purpose
At present, concomitant avascular necrosis (AVN) of femoral head and septic arthritis (SA) as a sequel of COVID-19 infection has yet not been documented. By large-scale use of life-saving corticosteroids (CS) in COVID-19 cases, our aim is to warn of the occurrence of hip joint infection in these patients.

Methods
We report a series of five cases in which patients developed septic arthritis concomitant with AVN after being treated for COVID-19 infection. The mean dose of prednisolone used in these cases was 1695.2 mg. The time period of onset of hip symptoms in our cases from the beginning of the COVID-19 infection was 56 days in the first case, 43 days in the second case, 30 days in the third case, 29 days in the fourth case and 50 days in the last case, with an average time of 41.6 days. All patients underwent surgery depending on the extent of articular cartilage damage by direct anterior approach.

Results
Clinical and laboratory symptoms improved significantly in all patients. The mean visual analogue pain score of the patients decreased from 9.4 (9–10) before surgery to 2.8 (1–4) after 1 week of operation.

Conclusion
In any patient with the history of COVID-19 infection specially those who have been treated with corticosteroid as one of the medications prescribed during the disease, any joint symptom specially in the hips should draw our attention to the joint infection, and with timely diagnosis and surgery, their hip joint can be saved.
AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives
Authors: Hanaford Allison R. , Cho Yoon-Jae , Nakai Hiroyuki 
Published: June 2022

AbstractMitochondrial diseases are a group of rare, heterogeneous diseases caused by gene mutations in both nuclear and mitochondrial genomes that result in defects in mitochondrial function. They are responsible for significant morbidity and mortality as they affect multiple organ systems and particularly those with high energy-utilizing tissues, such as the nervous system, skeletal muscle, and cardiac muscle. Virtually no effective treatments exist for these patients, despite the urgent need. As the majority of these conditions are monogenic and caused by mutations in nuclear genes, gene replacement is a highly attractive therapeutic strategy. Adeno-associated virus (AAV) is a well-characterized gene replacement vector, and its safety profile and ability to transduce quiescent cells nominates it as a potential gene therapy vehicle for several mitochondrial diseases. Indeed, AAV vector-based gene replacement is currently being explored in clinical trials for one mitochondrial disease (Leber hereditary optic neuropathy) and preclinical studies have been published investigating this strategy in other mitochondrial diseases. This review summarizes the preclinical findings of AAV vector-based gene replacement therapy for mitochondrial diseases including Leigh syndrome, Barth syndrome, ethylmalonic encephalopathy, and others.
Identification of novel non-HFE mutations in Chinese patients with hereditary hemochromatosis
Authors: Zhang Wei , Li Yanmeng , Xu Anjian , Ouyang Qin , Wu Liyan , Zhou Donghu , Wu Lina , Zhang Bei , Zhao Xinyan , Wang Yu , Wang Xiaoming , Duan Weijia , Wang Qianyi , You Hong , Huang Jian , Ou Xiaojuan , Jia Jidong ,   China Registry of Genetic/Metabolic Liver Diseases (CR-GMLD) Group
Published: June 2022

Abstract
Backgrounds
Hereditary hemochromatosis (HH) is mainly caused by homozygous p.C282Y mutations in HFE in the Caucasians. We recently reported non-HFE mutations constitute the major cause of HH in Chinese. However, there is still a relatively high proportion of cases with primary iron overload from unexplained causes. We aimed to explore novel non-HFE mutations in Chinese patients with primary iron overload.

Methods
Whole exome sequence was conducted to screen mutations in novel HH-related genes in the 9 cases with unexplained primary iron overload. Then the representative candidate genes were screened for mutations in another cohort of 18 HH cases. The biological function of the selected genes and variants were analyzed in vitro.

Results
Whole exome sequencing of 9 cases with unexplained primary iron overload identified 42 missense variants in 40 genes associated with iron metabolism pathway genes such as UBE2O p.K689R and PCSK7 p.R711W. Subsequent Sanger sequencing of the UBE2O and PCSK7 genes in the 27 cases with primary iron overload identified p.K689R in UBE2O, p.R711W and p.V143F in PCSK7 at frequency of 2/27,1/27 and 2/27 respectively. In vitro siRNA interference of UBE2O and PCSK7 resulted in down-regulated HAMP mRNA expression. Adenovirus generation of UBE2O p.K689R in cell lines resulted in increased expression of SMAD6 and SMAD7 and downregulation of p-SMAD1/5 and HAMP expression, and the reduction of hepcidin level.

Conclusions
Our study identified a series of novel candidate non-HFE mutations in Chinese patients with HH. These may provide insights into the genetic basis of unexplained primary iron overload.
HIV-related lung cancer in Uganda: a cohort study
Authors: Baluku Joseph Baruch , Bogere Naghib , Namiiro Sharon , Walusansa Victoria , Andia-Biraro Irene , Worodria William , Kirenga Bruce 
Published: June 2022

Abstract
Background
There are few reports on lung cancer among people with HIV (PWH) in Sub-Saharan Africa. In this report, we describe a cohort of PWH and lung cancer at the Uganda Cancer Institute.

Methods
This retrospective cohort of PWH and lung cancer was managed at the Uganda Cancer Institute between 2008 and 2018. Sociodemographic and clinical data were abstracted from the patient charts. The median survival from diagnosis to death, loss-to-follow up or 31st December 2018, was estimated.

Results
There were 18 people with HIV and lung cancer. The median (interquartile range, IQR) age was 49.5 (38.8–56.0) years, 11 (61.1%) were women and 5 (27.8%) were smokers. Of the 18 PWH, 13 (72.2%) were on antiretroviral therapy and the median (IQR) CD4 count (n = 13) was 380 (243.5–595) cells per mm3. Difficulty in breathing (88.9%), chest pain (78.6%, n = 11), cough (76.5%, n = 17) and weight loss (72.2%) were the commonest symptoms while pleural effusions were observed in 12 (66.7%). In this cohort, 8 (44.4%) were presumptively treated for tuberculosis before the diagnosis of lung cancer. Seven (38.9%) had an Eastern Cooperative Oncology Group performance status of 3. Non-small cell lung cancer was the predominant histological type observed in 17 (94.4%) of whom 14 (82.4%) had adenocarcinoma. Majority of PWH had stage IV disease (88.9%). The median (IQR) survival was 3.3 (1.1–13.2) months and all were either dead (72.2%) or lost-to-follow up (27.8%) at five years from diagnosis.

Conclusion
People with HIV and lung cancer in Uganda report low rates of smoking, present with advanced disease and post very poor survival rates. There is need for biomarkers for early detection of lung cancer in HIV.
Therapeutic effects and central mechanism of acupuncture and moxibustion for treating functional dyspepsia: study protocol for an fMRI-based randomized controlled trial
Authors: Zhang Pan , Yin Tao , Mao Yang-Ke , He Zhao-Xuan , Yang Sha , Huang Si-Qin , Sun Rui-Rui , Zeng Fang 
Published: June 2022

Abstract
Background
Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear.

Methods
This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes.

Discussion
We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD.

Trial registration
Chinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR2100049496. Registered on 2 August 2021
Regulating clinical trials in a resource-limited setting during the Ebola public health emergency in Sierra Leone
Authors: Abiri Onome T. , Bah Abdulai J. , Lahai Michael , Lisk Durodami R. , Komeh James P. , Johnson Joy , Johnson Wiltshire C. N. , Mansaray Sheku S. , Kanu Joseph Sam , Russell James B. W. , Thomas Fawzi , Sesay Murtada M. , Conteh Thomas A. , Tejan-Kella Alphan , Sesay Mohamed , Ghazzawi Manal , Thompson Brian , Conteh Sorie , Deen Gibrilla Fadlu 
Published: June 2022

AbstractClinical trials during public health emergencies of novel medical products such as therapeutics and vaccines in resource-limited settings are daunting due to the limited capacity for regulatory assessment. Regulating clinical trials during the Ebola outbreak in Sierra Leone required expedited evaluation to identify medical products that could be promptly introduced to combat the epidemic in the absence of approved treatment or prevention. This article explored the decisions taken by the Pharmacy Board of Sierra Leone through its Expert Committee on Medicine Safety and Clinical Trials regarding clinical trials oversight during the Ebola epidemic and the lessons learned. This independent expert committee assessed and provided scientific opinions to the Pharmacy Board of Sierra Leone to inform approval of all clinical trials within 10–15 working days. We also requested for assisted review from the African Vaccine Regulatory Forum and support from the US Food and Drug Administration through a unilateral recognition and reliance memorandum of understanding. In addition, the Agency-ensured structures and systems were in place for reporting and reviewing adverse events and serious adverse events, management of biological samples, submission and review of progress reports, and good clinical practice inspections. Unfortunately, the Ebola epidemic revealed many weaknesses in the country’s clinical trials regulatory structure and processes. Government and partners should further offer more resources to build the clinical trial structures and systems so that the Agency will be better poised to handle future public health emergencies.
Levofloxacin versus clarithromycin for Helicobacter pylori eradication: are 14 day regimens better than 10 day regimens?
Authors: Azab Eman T. , Thabit Abrar K. , McKee Sean , Al-Qiraiqiri Aymen 
Published: June 2022

Abstract
Background
Helicobacter pylori eradication by the conventional clarithromycin therapy has largely dropped in the recent years possibly due to antimicrobial resistance. Hence, levofloxacin-based regimen has been used as salvage therapy. However, data regarding its effectiveness on eradication are controversial. This study aimed to compare the eradication rate of levofloxacin-based regiment to that of the conventional first-line clarithromycin regimen.

Methods
Patients diagnosed with H. pylori infection and treated with levofloxacin triple therapy or clarithromycin-based regimen for 10 or 14 days were included. Patients were excluded if they used antibiotics or proton pump inhibitors within 4 or 2 weeks, respectively, of the H. pylori eradication confirmation test. H. pylori eradication rate was assessed, as well as the impact of diabetes and esophagogastroduodenoscopy (EGD) findings.

Results
Of 245 patients, 145 were in the levofloxacin group and 100 in the clarithromycin group. Most patients in either group received therapy for 14 days vs. 10 days (P = 0.002). Levofloxacin-based treatment was associated with a higher eradication rate compared with clarithromycin-based treatment (74.5 vs. 62%, respectively; P = 0.04). The 14 day levofloxacin-based regimen resulted in the highest eradication rate, followed by the 14 day regimen of clarithromycin (80.9 vs. 66.3%; P = 0.03). The 10 day regimens exhibited 62.7 and 41.2% eradication rates, respectively (P = 0.12). H. pylori eradication was not affected by diabetes or EGD findings (P = 0.98 and 0.3, respectively).

Conclusions
Results from this study support the use of a levofloxacin-based regimen as a first-line therapy in the treatment of H. pylori infection for 14 days regardless of diabetes and EGD findings.
Mountain pass solution for the weighted Dirichlet $(p(z),q(z))$-problem
Authors: Alharthi Nadiyah Hussain , Albalawi Kholoud Saad , Vetro Francesca 
Published: June 2022

AbstractWe consider the Dirichlet boundary value problem for equations involving the $(p(z),q(z))$
(
p
(
z
)
,
q
(
z
)
)
-Laplacian operator in the principal part on an open bounded domain $\Omega \subset \mathbb{R}^{n}$
Ω
⊂

R
n

. Here, the $p(z)$
p
(
z
)
-Laplacian is weighted by a function $a \in L^{\infty}(\Omega )_{+}$
a
∈

L
∞

(
Ω
)

+

, and the nonlinearity in the reaction term is allowed to depend on the solution without imposing the Ambrosetti–Rabinowitz condition. The proof of the existence of solution to our problem is based on a mountain pass critical point approach with the Cerami condition at level c.
Spatial variation and determinates of dietary diversity among children aged 6–23 months in Ethiopia: spatial and multilevel analysis using Ethiopian Demography Health Survey (EDHS) 2019
Authors: Alemu Tewodros Getaneh , Techane Masresha Asmare , Wubneh Chalachew Adugna , Assimamaw Nega Tezera , Belay Getaneh Mulualem , Tamir Tadesse Tarik , Muhye Addis Bilal , Kassie Destaye Guadie , Wondim Amare , Terefe Bewuketu , Tarekegn Bethelihem Tigabu , Ali Mohammed Seid , Fentie Beletech , Gonete Almaz Tefera , Tekeba Berhan , Kassa Selam Fisiha , Desta Bogale Kassahun , Ayele Amare Demsie , Dessie Melkamu Tilahun , Atalell Kendalem Asmare 
Published: June 2022

Abstract
Background
Minimum dietary diversity is the consumption of five or more food groups from the eight World Health Organization recommended food groups. Adequately diversified diet, in terms of amount and composition, is critical for optimal growth, development, and long-term health outcomes in the first 2 years. Understanding the regional variation of dietary diversity and the underlying factors is crucial for developing and implementing interventions. However, the use of spatial approaches in dietary studies has not been widely established. Therefore, this study aimed to explore the spatial patterns and determinates of minimum dietary diversity practice among 6–23 months children in Ethiopia.

Methods
Secondary data analysis was conducted based on the Demographic and Health Surveys data conducted in Ethiopia. A total weighted sample of 1578 children aged 6–23 months was included for this study. The Global Moran’s I was estimated to look into the regional variation of dietary diversity and hotspot and cold spot areas. Further, multivariable multilevel logistic regression was used for factor analyses. Adjusted Odds Ratio with 95% CI was used to declare the strength and significance of the association.

Results
Overall, 87.4% (95% CI: 85.7 to 88.9%) of children in 2019 had inadequate Minimum dietary diversity. We identified statistically significant clusters of high inadequate dietary diversity (hotspots) notably observed in Somali, Afar, Eastern and western Amhara, western Tigray, Benishangul, and Northeastern and western parts of the southern nations, nationality and peoples’ regions. Inadequate dietary diversity was significantly higher among young children, uneducated mother, married women, younger mother, no postnatal check, community with higher level of poverty and community level uneducated woman.

Conclusion
According to the findings of this study inadequate Minimum dietary diversity for children as measured by World Health Organization dietary assessment shows high. Children's dietary diversity was distributed non-randomly in different districts across Ethiopia's regions. The findings of the study provided critical evidence about dietary diversity and associated factors. Hence, policy should focused on improve education status of Mother, boosting economic status of the community, increased maternal continuum of care and focused on young children nutrition may advance dietary diversity.
5-Methoxytryptophan pretreatment alleviates lipopolysaccharide-induced cardiac injury and dysfunction
Authors: Fu Yang , Dong Yi-Fei 
Published: June 2022

AbstractReducing inflammation is a promising therapeutic approach for sepsis-induced cardiomyopathy (SIC). The 5-Methoxytryptophan (5-MTP) is a tryptophan metabolite that demonstrates anti-inflammatory, anti-fibrosis, anti-tumorigenesis, and anti-senescence features. Current investigations aimed to assess the 5-MTP pretreatment impacts on lipopolysaccharide (LPS)-induced cardiac injury and dysfunction. For in vivo studies, the mice were categorized randomly into four groups: control, LPS, LPS+5-MTP (25 mg/kg) and LPS+5-MTP (50 mg/kg). The mice in the LPS+5-MTP groups were given 5-MTP intraperitoneally once a day for 7 days. LPS (10 mg/kg) was then administered intraperitoneally for 24 h. Echocardiography, cardiac injury biomarkers, and H & E staining evaluated heart anatomy and function. The findings indicate that 5-MTP pretreatment significantly reduced LPS-induced heart dysfunction and morphological alterations. Western blot assay was used for investigating molecular mechanisms. After LPS stimulation, the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) protein levels increased while anti-inflammatory cytokine (IL-10) decreased; however, 5-MTP pretreatment mitigated this response by suppressing the stimulation of the NF-κB signaling pathway. Furthermore, 5-MTP administration reduced LPS-induced cardiac apoptosis, as demonstrated by increased protein levels of cleaved-Casepase-1, cleaved-Casepase-3 and Bax, and decreased protein level of Bcl-2 after LPS stimulation, whereas LPS-induced cardiac apoptosis was reversed by 5-MTP pretreatment. In vitro, 5-MTP pretreatment had a similar cardioprotective effect on cultured cardiac fibroblasts challenged with LPS. In conclusion, 5-MTP pretreatment can reduce LPS-induced cardiac inflammation and apoptosis, implying that 5-MTP is a possible therapeutic option for SIC.
Development of a multi faceted platform containing a tetrazine, fluorophore and chelator: synthesis, characterization, radiolabeling, and immuno-SPECT imaging
Authors: McDonagh Anthony W. , McNeil Brooke L. , Rousseau Julie , Roberts Ryan J. , Merkens Helen , Yang Hua , Bénard François , Ramogida Caterina F. 
Published: June 2022

Abstract
Background
Combining optical (fluorescence) imaging with nuclear imaging has the potential to offer a powerful tool in personal health care, where nuclear imaging offers in vivo functional whole-body visualization, and the fluorescence modality may be used for image-guided tumor resection. Varying chemical strategies have been exploited to fuse both modalities into one molecular entity. When radiometals are employed in nuclear imaging, a chelator is typically inserted into the molecule to facilitate radiolabeling; the availability of the chelator further expands the potential use of these platforms for targeted radionuclide therapy if a therapeutic radiometal is employed. Herein, a novel mixed modality scaffold which contains a tetrazine (Tz)––for biomolecule conjugation, fluorophore—for optical imaging, and chelator—for radiometal incorporation, in one construct is presented. The novel platform was characterized for its fluorescence properties, radiolabeled with single-photon emission computed tomography (SPECT) isotope indium-111 (111In3+) and therapeutic alpha emitter actinium-225 (225Ac3+). Both radiolabels were conjugated in vitro to trans-cyclooctene (TCO)-modified trastuzumab; biodistribution and immuno-SPECT imaging of the former conjugate was assessed.

Results
Key to the success of the platform synthesis was incorporation of a 4,4′-dicyano-BODIPY fluorophore. The route gives access to an advanced intermediate where final chelator-incorporated compounds can be easily accessed in one step prior to radiolabeling or biomolecule conjugation. The DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) conjugate was prepared, displayed good fluorescence properties, and was successfully radiolabeled with 111In & 225Ac in high radiochemical yield. Both complexes were then separately conjugated in vitro to TCO modified trastuzumab through an inverse electron demand Diels–Alder (IEDDA) reaction with the Tz. Pilot small animal in vivo immuno-SPECT imaging with [111In]In-DO3A-BODIPY-Tz-TCO-trastuzumab was also conducted and exhibited high tumor uptake (21.2 ± 5.6%ID/g 6 days post-injection) with low uptake in non-target tissues.

Conclusions
The novel platform shows promise as a multi-modal probe for theranostic applications. In particular, access to an advanced synthetic intermediate where tailored chelators can be incorporated in the last step of synthesis expands the potential use of the scaffold to other radiometals. Future studies including validation of ex vivo fluorescence imaging and exploiting the pre-targeting approach available through the IEDDA reaction are warranted.