bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of lipodystrophy and metabolic disorders in patients starting non-nucleoside reverse transcriptase inhibitors in Benin
Authors: Zannou Djimon Marcel , Denoeud Lise , Lacombe Karine , Amoussou-Guenou Daniel , Bashi Jules , Akakpo Jocelyn , Gougounon Alice , Akondé Alain , Adè Gabriel , Houngbé Fabien , Girard Pierre-Marie 
Published: April 2022

Background The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented. Methods This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy. Results After a median follow-up of 23.2 months (interquartile range 22.3–23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15–2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33–1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22–0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28–1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5–307.4]; P=0.006) were significantly associated with lipohypertrophy. Conclusions Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART.
Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env
Authors: Mens Helene , Jørgensen Louise Bruun , Kronborg Gitte , Schønning Kristian , Benfield Thomas 
Published: April 2022

Background Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure. Methods Individuals with MDR HIV-1 receiving therapy for ≥3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate viral replication. Results Of 1,000 patients treated between 1995 and 2003, 72 individuals fulfilled the definition for triple-class failure, but 25 were non-compliant, 21 were successfully resuppressed and 3 had died or quit therapy. Of the 23 that fulfilled study criteria, 16 had samples available for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response ( P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes ( r=-0.56, P=0.04 and r=-0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes ( r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0.02). Conclusions Our results suggest that minor PI mutations and NRTI mutations present early during therapy failure are predictive of the CD4+ T-cell count slopes. Synonymous mutation rates of the env gene suggested that underlying differences in fitness could cause this association.
Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)-infected cells in patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis
Authors: Nishiura Yoshihiro , Nakamura Tatsufumi , Fukushima Naomi , Nakamura Hideki , Ida Hiroaki , Aramaki Toshiyuki , Eguchi Katsumi 
Published: April 2022

Background This study was conducted to construct a basis for a therapeutic strategy against human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained a disulfide moiety, prosultiamine, which is a homologue of allithiamine originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I-infected cells. Methods First, we analysed the apoptotic pathway in allicin or prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro treatment and in a clinical trial in HAM/TSP patients by quantitative PCR analysis of HTLV-I proviral load. Results Prosultiamine, like allicin, induced caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1 cells with prosultiamine treatment suggested that prosultiamine can induce caspase-dependent apoptosis through the mitochondrial pathway. On the basis of data showing that prosultiamine in vitro treatment against peripheral blood CD4+ T-cells of HAM/TSP patients induced a significant decrease of HTLV-I proviral copy numbers by apoptosis of HTLV-I- infected cells, we treated six HAM/ TSP patients with intravenous administration of pro-sultiamine for 14 days. As a result of this treatment, the copy numbers of HTLV-I provirus in peripheral blood decreased to approximately 30–50% of their pretreat-ment levels with some clinical benefits in all patients. Conclusions Our results suggest that prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I-infected cells in HAM/TSP.
Conserved domains and structure prediction of human cytomegalovirus UL27 protein
Authors: Hantz Sébastien , Couvreux Anthony , Champier Gaël , Trapes Laurène , Cotin Sébastien , Denis François , Bouaziz Serge , Alain Sophie 
Published: April 2022

Background The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine–threonine kinase, UL97 protein (pUL97). Because maribavir- resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear. Methods As there is no available crystal structure for pUL27 or any known structures of its homologous proteins, we attempted to identify pUL27 functional domains by sequence analysis, identification of conserved domains, structure prediction and matching with previously known maribavir resistance mutations. Results The UL27 sequence analysis of 20 HCMV wild-type strains and 8 ganciclovir-resistant HCMV strains allowed us to describe four conserved domains, to localize the putative phosphorylation sites and to identify protein–protein interface domains, suggesting that pUL27 could interact with either pUL97 or itself. Conclusions Although the function of pUL27 is still unknown in the HCMV replication cycle, our approach identified target domains that appeared to be essential to the function of pUL27. This work provides a better understanding on the relative importance of each pUL27 mutation and could form the basis of later comparison analyses, when a three-dimensional structure of a pUL27 homologue will be available.
Extracellular signal-regulated kinase phosphorylation enhancement and NaV1.7 sodium channel upregulation in rat dorsal root ganglia neurons contribute to resiniferatoxin-induced neuropathic pain: The efficacy and mechanism of pulsed radiofrequency therapy
Authors: Hidaka Kotaro , Maruta Toyoaki , Koshida Tomohiro , Kurogi Mio , Kage Yohko , Kouroki Satoshi , Shirasaka Tetsuro , Takeya Ryu , Tsuneyoshi Isao 
Published: April 2022

Pulsed radiofrequency (PRF) therapy is one of the most common treatment options for neuropathic pain, albeit the underlying mechanism has not been hitherto elucidated. In this study, we investigated the efficacy and mechanism of PRF therapy on resiniferatoxin (RTX)-induced mechanical allodynia, which has been used as a model of postherpetic neuralgia (PHN). Adult male rats were intraperitoneally injected with a vehicle or RTX. Furthermore, PRF current was applied on a unilateral sciatic nerve in all RTX-treated rats. On both ipsilateral and contralateral sides, the paw mechanical withdrawal thresholds were examined and L4-6 dorsal root ganglia (DRG) were harvested. In the DRG of rats with RTX-induced mechanical allodynia, NaV1.7, a voltage-gated Na+ channel, was upregulated following the enhancement of extracellular signal-regulated kinase phosphorylation. Early PRF therapy, which was applied 1 week after RTX exposure, suppressed this NaV1.7 upregulation and showed an anti-allodynic effect; however, late PRF therapy, which was applied after 5 weeks of RTX exposure, failed to inhibit allodynia. Interestingly, late PRF therapy became effective after daily tramadol administration for 7 days, starting from 2 weeks after RTX exposure. Both early PRF therapy and late PRF therapy combined with early tramadol treatment suppressed NaV1.7 upregulation in the DRG of rats with RTX-induced mechanical allodynia. Therefore, NaV1.7 upregulation in DRG is related to the development of RTX-induced neuropathic pain; moreover, PRF therapy may be effective in the clinical management of patients with PHN via NaV1.7 upregulation inhibition.
How should interventions to treat hand oedema be delivered? An online Delphi Consensus Method
Authors: Miller Leanne K , Jerosch-Herold Christina , Shepstone Lee 
Published: April 2022

Introduction Hand oedema (swelling) is a common consequence of hand trauma or surgery, but there is little agreement on how interventions to treat hand oedema should be delivered in practice. The purpose of this study was to engage a group of self-identified hand therapy experts to develop consensus on how four commonly used oedema management treatments should be implemented, which could be used in clinical practice or future clinical trials. Method A web-based Delphi study was conducted with eight volunteer hand therapists who met the pre-defined eligibility criteria for an ‘expert’ and were members of the British Association of Hand Therapists (BAHT). An a priori level of agreement was set at 75%. Interventions requiring consensus were decided on as a result of a previous national survey of practice and consisted of compression, elevation, massage and kinesiology tape. Results A total of 25 items were discussed across 3 rounds. This ranged from 23 items in round 1, to three items in round 3. In round 1, consensus was reached on 7/23 (30%) items. The required 75% consensus was reached on 14 items in round 2 and 1/3 items achieved consensus in round 3. Massage was the only treatment that required a third round. Discussion Consensus was reached on intervention description for three of the four modalities including the materials used (what), method of application including duration and frequency (when and how much) and tailoring or modifications. Two questions relating to massage did not reach the required consensus threshold and a majority agreement was accepted. The small panel size is a limitation and may affect the credibility of the consensus reached.
Renal abscess in children: Is size an important determinant in deciding treatment options?
Authors: Jain Prashant , Prasad Ashish , Sharma Rachna , Jain Sarika 
Published: April 2022

Background: Renal abscess (RA) is rarely seen in the paediatric age group. The proposed management protocols are mainly derived from the adult series which may not be appropriate in children. Objective: In this retrospective analysis of cases with renal and perinephric abscesses, the objective is to correlate the clinical presentation, radiological findings and treatment options and also to propose a paediatric-specific practical management algorithm. Study design: This is a retrospective study of cases with renal and perinephric abscesses admitted between March 2012 and February 2020. The patients were reviewed for demographics, presentation, predisposing factors, laboratory investigations, imaging, management and outcome. Results: Analysis of 12 paediatric patients (13 renal units) with RA (median age 4 years) was done. Organisms were isolated in 8 of 12 (66.6%) patients with Gram-negative organisms being the commonest. On admission, all patients were started on empirical broad-spectrum antibiotics. Except for two patients who were critically ill with frank sepsis and had a tender renal lump, the rest of them were initially offered conservative management with intravenous antibiotics, and the response was reviewed after 48–72 hours. Of five units with abscess size of ⩽3 cm, two units (40%) responded to conservative management, while three units (60%) required intervention, and of eight units of size >3 cm, three units (37.5%) responded to conservative management and five units (62.5%) required intervention. None of the abscesses with perinephric collection (30.7%) responded to antibiotics and required intervention. Conclusion: A protocol based on the size of RA as recommended in most of the adult series may not be appropriate in the paediatric age group because of the differences in clinical presentation, predisposing factors and immune response. The clinical condition on presentation, response to antibiotic therapy and the presence of perinephric collection should be considered as an important determinant in deciding the need for intervention. Level of evidence: 4
Effects of Perioperative Fascia Iliaca Compartment Block on Postoperative Pain and Hip Function in Elderly Patients With Hip Fracture
Authors: Hao Chao , Li Chao , Cao Ruiqi , Dai Yike , Xu Chongyang , Ma Lifeng , Guo Ai , Yu Haomiao 
Published: April 2022

Purpose Pain management is a challenging issue in elderly patients with hip fracture. Despite the accepted clinical outcomes following hip surgery, pain and prolonged recovery time are the most difficult consequences associated with the rehabilitation process. The purpose of this study was to evaluate pain relief and functional improvement associated with the Fascia Iliaca Compartment Block (FICB) during the perioperative period of elderly patients with hip fracture. Patients and methods This study included 120 elderly patients with hip fracture, who were admitted to our institution between January 2019 and December 2020. The participants were subsequently randomly divided into the routine analgesia (RA) and fascia iliaca compartment block (FICB) groups. Inter-group differences were compared via VAS scores at rest and during movement, Harris hip scores (HHS), presence of complications, adverse events after surgery, and length of hospital stay. Results The FICB group VAS scores at rest at 6 hour, 1 and 3 days, and 1 week after surgery were significantly lower than the RA group ( P < .05). Moreover, the FICB group VAS scores with movement were markedly lower at 6 hour, 1 and 3 days, as well as 1 and 2 weeks after surgery ( P < .05). The HHS of the FICB and RA groups were (53.41±8.63) and (40.02±9.61), respectively, on the seventh day after surgery, and the difference was statistically significant ( P < .05). The incidence of postoperative complications and adverse events in the FICB group were not statistically different from the RA group. The average hospital stay of the FICB group was 2.12 days shorter than the RA group, but the difference did not reach statistical significance ( P = .13). Conclusion FICB provides superior analgesic effect both at rest and with movement, along with rapid short-term recovery of hip function following surgery in elderly patients with hip fracture, without increasing postoperative complications or adverse events.
Patient-specific comorbidities as prognostic variables for survival in myelofibrosis
Authors: Sochacki Andrew L. , Bejan Cosmin Adrian , Zhao Shilin , Patel Ameet , Kishtagari Ashwin , Spaulding Travis P. , Silver Alexander J. , Stockton Shannon S. , Pugh Kelly , Dorand R. Dixon , Bhatta Manasa , Strayer Nicholas , Zhang Siwei , Snider Christina A. , Stricker Thomas , Nazha Aziz , Bick Alexander G. , Xu Yaomin , Savona Michael R. 
Published: April 2022

Abstract
Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt’s Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P = .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P = 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI, 7.2-235.2; P = 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P = .0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.
Role of APOA1 in the resistance to platinum-based chemotherapy in squamous cervical cancer
Authors: He Yue , Han Su-Bin , Liu Yang , Zhang Jing-Jing , Wu Yu-Mei 
Published: April 2022

Abstract
Background
To investigate the mechanism by which apolipoprotein A1 (APOA1) enhances the resistance of cervical squamous carcinoma to platinum-based chemotherapy.

Methods
Two cervical squamous carcinoma cell lines (SiHa and Caski) overexpressing APOA1 were constructed, treated with carboplatin, and compared to normal control cells.

Results
In both SiHa and Caski cell lines, the clone-forming ability of CBP-treated cells was lower than that of untreated cells, and the change in the number of clones of overexpressing cells was lower than that of normal control cells (p < 0.05), indicating that APOA1 overexpression enhanced chemoresistance. A screen for APOA1 downstream proteins affecting platinum-based chemoresistance using Tandem Mass Tag revealed 64 differentially expressed proteins in SiHa cells, which were subjected to Gene Ontology (annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, subcellular localization, structural domain annotation and enrichment, clustering, and interaction network analyses. Sixty-four differentially expressed proteins matching cancer-relavent association terms were screened and parallel response monitoring identified 29 proteins as possibly involved in the mechanism of platinum-based chemoresistance.

Conclusions
Our analysis suggested that the mechanism may involve numerous regulatory pathways, including promoting tumor growth via the p38 MAPK signaling pathway through STAT1, promoting tumor progression via the PI3K signaling pathway through CD81 and C3, and promoting resistance to platinum-based chemotherapy resistance through TOP2A. The present study aimed to preliminarily explore the function and mechanism of APOA1 in platinum-based chemoresistance in cervical cancer, and the detailed mechanism needs to be further studied.
Application of prechop technique in phacoemulsification for cataract patients with highly liquefied vitreous: a retrospective study
Authors: Zhao Jing , Li Zhouyue , Liu Yu , Han Xiaotong , Huang Shengsong 
Published: April 2022

Abstract
Background
Phacoemulsification using phaco-chop technique has many challenging features in cataract patients with highly liquefied vitreous. This study aimed to compare the intraoperative parameters and safety between prechop technique and traditional phaco-chop in phacoemulsification for these patients.

Methods
A total of 54 eyes of 54 patients with high myopia-related or post-vitrectomy cataract that underwent phacoemulsification combined with intraocular lens implantation were included in this retrospective study. Of them, 25 eyes that received manual prechop were included in the prechop group, and 29 eyes with best match of age, axial length and nuclear opalescence (NO) that received standardized phaco-chop were included as the control group. The intraoperative complications and surgery parameters were compared between groups.

Results
No surgical complications were observed in the prechop group, while 2 eyes with posterior capsular rupture and 1 eye with a broken ciliary zonule (10.3%) were found in the control group. There was no significant difference in phaco time, average energy, and cumulative dissipated energy (CDE) between groups (all P > 0.05), but for hard nuclear cataracts with NO grading ≥ 5, prechop group required less phaco time (P = 0.008) and CDE (P = 0.029). There were significant correlations between phaco time vs. NO (r = 0.762 vs. 0.581, both P < 0.005) and CDE vs. NO (r = 0.717 vs. 0.668, both P < 0.001) in the prechop group and control group, respectively.

Conclusions
The prechop technique which seemed to have less intraoperative complications, reduced phaco time and CDE compared to standardized phaco-chop might be a good alternative for cataract patients with highly liquefied or vitrectomized vitreous, especially those with hard nuclear cataracts.