bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dermatoscopy and Optical Coherence Tomography in Vulvar High-Grade Squamous Intraepithelial Lesions and Lichen Sclerosus: A Prospective Observational Trial
Authors: Huisman Bertine W. , Pagan Lisa , Naafs Rosanne G.C. , ten Voorde Wouter , Rissmann Robert , Piek Jurgen M.J. , Damman Jeffrey , Juachon Maria J. , Osse Michelle , Niemeyer-van der Kolk Tessa , van Hees Colette L.M. , van Poelgeest Mariette I.E. 
Published: March 2023

Objective
This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin.

Methods
A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin. Morphologic features of vHSIL and LS were compared with healthy controls. Epidermal thickness and blood flow were determined using D-OCT. Patients reported tolerability of each study procedure, including reference vulvar biopsies. The main outcome measures were feasibility and tolerability of imaging modalities, dermatoscopy and OCT characteristics, OCT epidermal thickness and D-OCT dermal blood flow.

Results
The application of dermatoscopy and D-OCT is feasible and tolerable. In vHSIL, dermatoscopic warty structures were present. In LS, sclerotic areas and arborizing vessels were observed. Structural OCT in the vulvar area aligned with histology for hyperkeratosis and dermal-epidermal junction visualization. Currently, the OCT algorithm is unable to calculate the epidermal thickness of the uneven vulvar area. Dynamic optical coherence tomography showed statistically significant increased blood flow in LS patients (mean ± SD, 0.053 ± 0.029) to healthy controls (0.040 ± 0.012; p = .0024).

Conclusions
The application of dermatoscopy and D-OCT is feasible and tolerable in vHSIL and LS patients. Using dermatoscopy and D-OCT, we describe potential characteristics to aid differentiation of diseased from healthy vulvar skin, which could complement clinical assessments.
Inclisiran: present and future perspectives of a new effective LDL cholesterol-lowering agent
Authors: Giordano Salvatore , Polimeni Alberto , Esposito Giovanni , Indolfi Ciro , Spaccarotella Carmen 
Published: March 2023

Purpose of review
To highlight critical aspects of inclisiran, from preclinical studies to current recommendations in clinical practice and future perspectives.

Recent findings
Inclisiran use has been recently approved by regulatory agencies. The evidence of its efficacy and safety makes it a promising therapeutical tool for treating dyslipidemias.

Summary
The link between LDL-cholesterol and atherosclerotic cardiovascular disease (ASCVD) is well established. Inclisiran, a small interfering RNA, has proven its safety and efficacy in reducing LDL-cholesterol, and FDA and EMA have recently approved its use. This review illustrates the development, structure, and mechanism of action of inclisiran and provides information regarding its efficacy, safety, and current recommendation in clinical practice. Moreover, it provides key information on the most recent/ongoing trials that will help us to implement the use of inclisiran in clinical practice.
Second Opinions for Patients With a Persistent Depressive Disorder: Effects on Severity of Depression and Quality of Life
Authors: de Vocht Anneke M.R. , Witteman Cillia L.M. , de Vocht Frank , Spijker Jan 
Published: March 2023

Background:
A persistent depressive disorder has a major impact on both patients and health care systems. Despite the advice in guidelines to seek a second opinion if there is insufficient evidence of recovery after treatment, and the great number of second opinions in psychiatric care for patients with persistent depression, only a few studies have been published about their effects.

Methods:
Multilevel analyses were conducted to compare the mean test scores of a group of patients with a persistent depressive disorder who received the intervention of a second opinion with scores from a matched control group, at 3 time points: baseline, intervention, and follow-up.

Results:
A significant decrease in the severity of depression 3 months after the second opinion was found. No effects on quality of life or treatment satisfaction were found.

Limitations:
The study sample was a convenience sample without randomization, and many values were missing in the data. In addition, a 3-month follow-up may have been too short to expect effects of the recommendations from the second opinion. The instructions concerning how to rate treatment satisfaction were also ambiguous.

Conclusions:
A second opinion can be of value for persistent depression. Further research should address the question of whether the effect that was found is caused by the second opinion itself or is the result of subsequent changes in treatment.
Ai Chi for Balance and Gait in Individuals with Parkinson's Disease: A Pilot Study
Authors: So Billy Chun Lung , Tse Daniel Hon Ting , Kwok Manny Man Ying 
Published: March 2023

Background and Purpose:
Parkinson disease (PD) has effects on an individual's balance, and Ai Chi can be used to improve balance and gait performance. The aim of this study was to investigate the effectiveness of Ai Chi in improving the balance and gait of individuals with idiopathic PD.

Method:
Ten individuals with PD at Hoehn and Yahr stages 1-3 were included in this 6-week study. Participants underwent a structured Ai Chi program (1 hour per session, twice weekly) for 6 weeks (12 sessions in total). Balance was assessed at baseline and week 6 using the Timed Up and Go (TUG) test, the Five Times Sit-to-Stand (FTSTS) test, the Four Square Step Test (FSST), the Ten Meter Walk Test (10MWT), and the Sensory Organization Test (SOT). Gait parameters were measured by inertial measurement units and videotaping for 2-dimentional motion analysis. Surface electromyography was used for measuring muscle activity during gait in the bilateral rectus femoris, biceps femoris, gastrocnemius, and tibialis anterior.

Results:
In a pre- and postintervention comparison, significant improvements were observed in the FTSTS, FSST, and TUG scores as well as in the composite, vision, and vestibular scores in the 10MWT and SOT (P < .005). The results indicated improvement in balance. As for the gait analysis, no significant differences were observed in spatiotemporal parameters, including speed, cadence, step length, stride length, step duration, stride duration, swing-phase duration, stance-phase duration, and double support duration. Insignificant changes in the percentage maximum voluntary contraction of all the muscles examined were found, while a significant decrease in maximum voluntary contraction was identified in the left biceps femoris.

Conclusions:
The Ai Chi program produced a significant improvement in balance in individuals with PD, with insignificant results shown in gait. Ai Chi is an appropriate intervention to improve balance in individuals with PD.
The AM-FM Study (Aquatic physiotherapy Management in FibroMyalgia): Exploring Patients' Perceptions About Aquatic Exercise in the Treatment and Management of Fibromyalgia
Authors: Merry Graham , Cairns Mindy C. 
Published: March 2023

Background and Purpose:
Fibromyalgia is a complex long-term condition characterized by widespread chronic pain, fatigue, and cognitive disturbances. Between 2.9% and 7% of the UK population may be affected. Hydrotherapy (therapeutic aquatic exercise) is frequently used in the management of fibromyalgia, and most research to date has compared hydrotherapy with a comparator or control group in controlled studies. No study has evaluated the role of hydrotherapy from the patient's perspective. The main purpose of the present study was to explore and examine the experiences and views of patients on hydrotherapy in the treatment and management of fibromyalgia.

Methods:
An online UK-wide survey was conducted with closed- and open-text answers using a convenience sample of participants with fibromyalgia with experience of hydrotherapy.

Results:
In total, 37 participants aged 25 to 79 years (M = 49.2 years) completed the survey; 34 (92%) participants were female, 3 (8%) were male, and 33 (89%) were of White ethnicity. Thirty-one (84%) participants reported hydrotherapy to be beneficial in their management, but 28 (76%) identified barriers to accessing suitable hydrotherapy facilities. Twenty-six (70%) respondents reported beneficial effects of hydrotherapy in relation to pain relief, 25 (68%) reported in relation to physical function, 23 (62%) reported in relation to promoting relaxation, and 21 (57%) reported in relation to an improved sense of well-being. Themes arising from free-text responses included beneficial effects for relaxation and sleep, positive attributes of the properties of the water, and patient preferences for hydrotherapy over land-based exercise.

Discussion and Conclusions:
The findings highlight beneficial effects of hydrotherapy beyond those of pain relief and improved physical function identified by previous studies including relaxation effects and positive effect on sleep, among others. Specific access factors may pose obstacles to continued self-directed hydrotherapy for some individuals.
Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy
Authors: Temu Tecla M. , Polyak Stephen J. , Wanjalla Celestine N. , Mandela Nelson Aringo , Dabee Smritee , Mogaka Jerusha N. , Masyuko Sarah , Longernecker Chris , Shakil Saate , Chohan Bhavna , Page Stephanie T. , Lacourse Sylvia M. , Gitura Bernard , Crothers Kristina , Oyugi Julius , Jaspan Heather , Farquhar Carey , Zifodya Jerry S. 
Published: March 2023

Background:
Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults.

Methods:
We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI−, HIV−LTBI+, HIV−LTBI−). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors.

Results:
Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models (P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants (P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV−LTBI− (P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4+ T-cell count and ART duration.

Conclusions:
Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.
The impact of attrition on the transmission of HIV and drug resistance
Authors: Shen Mingwang , Xiao Yanni , Rong Libin , Zhuang Guihua , Song Chang , Zhao Quanbi , Huang Jinghua , Zhu Qiuying , Liang Shujia , Chen Huanhuan , Li Jianjun , Liao Lingjie , Shao Yiming , Xing Hui , Ruan Yuhua , Lan Guanghua 
Published: March 2023

Background:
Attrition due to loss to follow-up or termination of antiretroviral therapy (ART) among HIV-infected patients in care may increase the risk of emergence and transmission of drug resistance (TDR), diminish benefit of treatment, and increase morbidity and mortality. Understanding the impact of attrition on the epidemic is essential to provide interventions for improving retention in care.

Methods:
We developed a comprehensive HIV transmission dynamics model by considering CD4+ cell count dependent diagnosis, treatment, and attrition involving TDR and acquired drug resistance. The model was calibrated by 11 groups HIV/AIDS surveillance data during 2008–2018 from Guangxi, China, and validated by the prevalence of TDR among diagnosed treatment-naive individuals. We aimed to investigate how attrition would affect the transmission of HIV and drug-resistance when expanding ART.

Results:
In the base case with CD4+ cell count dependent per capita attrition rates 0.025∼0.15 and treatment rates 0.23∼0.42, we projected cumulative total new infections, new drug-resistant infections, and HIV-related deaths over 2022–2030 would be 145 391, 7637, and 51 965, respectively. Increasing treatment rates by 0.1∼0.2 can decrease the above total new infections (deaths) by 1.63∼2.93% (3.52∼6.16%). However, even 0.0114∼0.0220 (0.0352∼0.0695) increase in attrition rates would offset this benefit of decreasing infections (deaths). Increasing treatment rates (attrition rates) by 0.05∼0.1 would increase the above drug-resistant infections by 0.16∼0.30% (22.18∼41.15%).

Conclusion:
A minor increase in attrition can offset the benefit of treatment expansion and increase the transmission of HIV drug resistance. Reducing attrition rates for patients already in treatment may be as important as expanding treatment for untreated patients.
The Ability of Comorbidity Indices to Predict Mortality After Heart Transplantation: A Validation of the Danish Comorbidity Index for Acute Myocardial Infarction, Charlson Comorbidity Index, and Elixhauser Comorbidity Index
Authors: Bonnesen Kasper , Mols Rikke E. , Løgstrup Brian , Gustafsson Finn , Eiskjær Hans , Schmidt Morten 
Published: March 2023

Background
Advanced heart failure patients often have comorbidities of prognostic importance. However, whether total pretransplantation comorbidity burden predicts mortality in patients treated with heart transplantation (HTx) is unknown. We used population-based hospital and prescription data to examine the ability of the Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI), DANCAMI restricted to noncardiovascular diseases, Charlson Comorbidity Index, and Elixhauser Comorbidity Index to predict 30-d, 1-y, 5-y, and 10-y all-cause and cardiovascular mortality after HTx.

Methods
We identified all adult Danish patients with incident HTx from the Scandiatransplant Database between March 1, 1995, and December 31, 2018 (n = 563). We calculated Harrell’s C-Statistics to examine discriminatory performance.

Results
The C-Statistic for predicting 1-y all-cause mortality after HTx was 0.58 (95% confidence interval [CI], 0.50-0.65) for a baseline model including age and sex. Adding comorbidity score to the baseline model did not increase the C-Statistics for DANCAMI (0.58; 95% CI, 0.50-0.65), DANCAMI restricted to noncardiovascular diseases (0.57; 95% CI, 0.50-0.64), Charlson Comorbidity Index (0.59; 95% CI, 0.51-0.66), or Elixhauser Comorbidity Index (0.58; 95% CI, 0.51-0.65). The results for 30-d, 5-y, and 10-y all-cause and cardiovascular mortality were consistent.

Conclusions.
After accounting for patient age and sex, none of the commonly used comorbidity indices added predictive value to short- or long-term all-cause or cardiovascular mortality after HTx.
MyKidneyCoach, Patient Activation, and Clinical Outcomes in Diverse Kidney Transplant Recipients: A Randomized Control Pilot Trial
Authors: Pollock McLean D. , Stauffer Nicolas , Lee Hui-Jie , Chow Shein-Chung , Satoru Ito , Moats Lynnette , Swan-Nesbit Sherri , Li Yan , Roberts John K. , Ellis Matthew J. , Diamantidis Clarissa J. , Docherty Sharron L. , Chambers Eileen T. 
Published: March 2023

Background:
Kidney transplant (KT) recipients who are not actively engaged in their care and lack self-management skills have poor transplant outcomes, which are disproportionately observed among Black KT recipients. This pilot study aimed to determine whether the MyKidneyCoach app, an mHealth intervention that provides self-management monitoring and coaching, improved patient activation, engagement, and nutritional behaviors in a diverse KT population.

Methods:
This was a randomized, age-stratified, parallel-group, attention-control, pilot study in post-KT patients. Participants were randomized into the attention-control with access to MyKidneyCoach for education and self-management (n = 9) or the intervention with additional tailored nurse coaching (n = 7). Feasibility, acceptability, and clinical outcomes were assessed.

Results:
The acceptability of MyKidneyCoach by System Usability Scale was 67.5 (95% confidence interval [CI], 59.1-75.9). Completion rates based on actively using MyKidneyCoach were 81% (95% CI, 57%-93%) and study retention rate of 73%. Patient activation measure significantly increased overall by a mean of 11 points (95% CI, 3.2-18.8). Additionally, Black patients (n = 7) had higher nutrition self-efficacy scores of 80.5 (95% CI, 74.4-86.7) compared with 75.6 (95% CI, 71.1-80.1) in non-Black patients (n = 9) but lower patient activation measure scores of 69.3 (95% CI, 56.3-82.3) compared with 71.8 (95% CI, 62.5-81) in non-Black patients after 3 mo.

Conclusions:
MyKidneyCoach was easy to use and readily accepted with low attrition, and improvements were demonstrated in patient-reported outcomes. Both Black and non-Black participants using MyKidneyCoach showed improvement in self-management competencies; thus, this intervention may help reduce healthcare inequities in KT.
Joint associations of pregnancy complications and postpartum maternal renal biomarkers with severe cardiovascular morbidities: A US racially diverse prospective birth cohort study
Authors: Hong Xiumei , Rosenberg Avi Z. , Heymann Jurgen , Yoshida Teruhiko , Waikar Sushrut S. , Ilori Titilayo O. , Wang Guoying , Rebuck Heather , Pearson Colleen , Wang Mei-Cheng , Winkler Cheryl A. , Kopp Jeffrey B. , Wang Xiaobin 
Published: March 2023

AbstractRationale & ObjectivePregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD.MethodsThis study included 576 mothers of diverse ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and cystatin C were measured 1-3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models.ResultsDuring an average of 10.3±3.2 years of follow-up, 34 mothers developed one or more CVD events. Although no significant associations were found between creatinine and risk of CVD, per unit increase of cystatin C (CysC) was associated with a hazard ratio (HR) of 5.21 (95%CI = 1.49-18.2) for CVD. A borderline significant interactive effect was observed between elevated CysC (≥75th percentile) and preeclampsia. Compared to those without preeclampsia and with normal CysC level (<75thpercentile), mothers with preeclampsia and elevated CysC had the highest risk of CVD (HR=3.8, 95%CI = 1.4-10.2), while mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery.ConclusionsIn this sample of US, traditionally under-represented multi-ethnic high-risk mothers, elevated maternal plasma cystatin C and pregnancy complications synergistically increased risk of CVD later in life. These findings warrant further investigation.Clinical PerspectivesWhat is new?Maternal postpartum elevated levels of cystatin C are independently associated with higher risk of cardiovascular diseases (CVD) later in life.Maternal pregnancy complications coupled with postpartum elevated levels of cystatin C synergistically increased future risk of CVD.What are the clinical implications?These findings, if further confirmed, suggest that women with pregnancy complications and elevated postpartum cystatin C may be at particular high risk for CVD later in life compared to women without these risk factors.
Global disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury
Authors: Yamaguchi Reona , Ueno Satoko , Kawasaki Toshinari , Chao Zenas C. , Mitsuhashi Masahiro , Isa Kaoru , Takei Tomohiko , Kobayashi Kenta , Takahashi Jun , Onoe Hirotaka , Isa Tadashi 
Published: March 2023

AbstractThe induction of large-scale plasticity in the adult brain should be key for recovery from severe damage of the central nervous system. Here, drastic motor recovery was observed after subhemisection spinal cord injury in macaques that received intensive training and cortical electrical stimulation. During recovery, movement-related activity increased in ipsilesional sensorimotor areas and functional connectivity from ipsilesional to contralesional areas was strengthened. Electrical stimulation applied widely across bilateral sensorimotor areas induced muscle twitches in affected and intact forelimbs. The interhemispheric inhibition observed before injury was switched to facilitation. Furthermore, massive re-routing occurred in corticospinal axons from the contralesional motor cortex. Such global disinhibition and massive plasticity would open the workspace for the reorganization of motor networks to recruit novel areas for recovery.One Sentence SummaryGlobal disinhibition and corticospinal plasticity for drastic recovery after spinal cord injury in macaque monkeys.
Fgf8regulates first pharyngeal arch segmentation through pouch-cleft interactions
Authors: Zbasnik Nathaniel , Fish Jennifer L. 
Published: March 2023

AbstractThe pharyngeal arches are transient developmental structures that, in vertebrates, give rise to tissues of the head and neck. A critical process underlying the specification of distinct arch derivatives is segmentation of the arches along the anterior-posterior axis. Out-pocketing of the pharyngeal endoderm between the arches is a key mediator of this process, and although it is essential, mechanisms regulating out-pocketing vary between pouches and between taxa. Here, we focus on the patterning and morphogenesis of epithelia associated with the first pharyngeal arch, the first pharyngeal pouch (pp1) and the first pharyngeal cleft (pc1), and the role ofFgf8dosage in these processes. We find that severe reductions ofFgf8levels disrupt both pp1 and pc1 development. Notably, out-pocketing of pp1 is largely robust toFgf8reductions, however, pp1 extension along the proximal-distal axis fails whenFgf8is low. Our data indicate that extension of pp1 requires physical interaction with pc1, and that multiple aspects of pc1 morphogenesis requireFgf8. In particular,Fgf8is required for specification of regional identity in both pp1 and pc1, for localized changes in cell polarity, and for elongation and extension of both pp1 and pc1. Overall, our data indicate a critical role for the lateral surface ectoderm in segmentation of the first pharyngeal arch that has previously been under-appreciated.