bluuebunny/crossref_metadata_2025 huggingface dataset:
Lenvatinib Combined With Transarterial Chemoembolization as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH)
Authors: Peng Zhenwei , Fan Wenzhe , Zhu Bowen , Wang Guoying , Sun Junhui , Xiao Chengjiang , Huang Fuxi , Tang Rong , Cheng Yu , Huang Zhen , Liang Yuchuang , Fan Huishuang , Qiao Liangliang , Li Fuliang , Zhuang Wenquan , Peng Baogang , Wang Jiping , Li Jiaping , Kuang Ming
Published: August 2022

PURPOSE

Lenvatinib (LEN) is a first-line therapy for patients with advanced hepatocellular carcinoma (HCC); however, it has shown modest survival benefits. Therefore, we aimed to compare clinical outcomes of LEN combined with transarterial chemoembolization (LEN-TACE) versus LEN monotherapy in patients with advanced HCC.

MATERIALS AND METHODS

This was a multicenter, randomized, open-label, parallel group, phase III trial. Patients with primary treatment-naive or initial recurrent advanced HCC after surgery were randomly assigned (1:1) to receive LEN plus on-demand TACE (LEN-TACE) or LEN monotherapy. LEN was initiated within 3 days after random assignment (initial dose: 12 mg once daily for patients ≥ 60 kg; 8 mg once daily for patients < 60 kg). TACE was initiated one day after LEN initiation. The primary end point was overall survival (OS).

RESULTS

Between June 2019 and July 2021, a total of 338 patients underwent random assignment at 12 centers in China: 170 to LEN-TACE and 168 to LEN. At a prespecified event-driven interim analysis after a median follow-up of 17.0 months, the median OS was significantly longer in the LEN-TACE group (17.8 v 11.5 months; hazard ratio, 0.45; P < .001). The median progression-free survival was 10.6 months in the LEN-TACE group and 6.4 months in the LEN group (hazard ratio, 0.43; P < .001). Patients in the LEN-TACE group had a higher objective response rate according to the modified RECIST (54.1% v 25.0%, P < .001). Multivariable analysis revealed that portal vein tumor thrombus and treatment allocation were independent risk factors for OS.

CONCLUSION

The addition of TACE to LEN improves clinical outcomes and is a potential first-line treatment for patients with advanced HCC.
A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes
Authors: Wang Chih-Yuan , Huang Kuo-Chin , Lu Chia-Wen , Chu Chih-Hsun , Huang Chien-Ning , Chen Harn-Shen , Lee I-Te , Chen Jung-Fu , Chen Ching-Chu , Chen Chung-Sen , Hsieh Chang-Hsun , Tien Kai-Jen , Chien Hung-Yu , Huang Yu-Yao , Hsu Jui-Pao , Shane Guang-Tzuu , Chang Ai-Ching , Wu Yen-Chieh , Sheu Wayne Huey-Herng
Published: August 2022

Context

There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic β-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of β-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment.

Objective

This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone.

Methods

Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment.

Results

A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (−0.36, P = 0.0373) and 450 mg/day (−0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-β score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial.

Conclusion

Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.
Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features
Authors: Chen Debbie W , Rob Farizah I , Mukherjee Rik , Giordano Thomas J , Haymart Megan R , Banerjee Mousumi
Published: August 2022

Context

Noninvasive encapsulated follicular variant of papillary thyroid cancer was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in January 2017. The impact of this nomenclature change at a population level remains unknown.

Objective

Examine use of NIFTP across different US regions and populations.

Design

Descriptive epidemiology study using SEER-22 data (2000-2019).

Participants

Individuals diagnosed with papillary or follicular thyroid cancer (2000-2019) or NIFTP (2017-2019).

Main Outcome Measures

Annual incidence rates of thyroid cancer by subtype and NIFTP. Using 2018-2019 data, (1) rates of NIFTP at the 17 SEER-22 sites and (2) comparison of demographics for patients diagnosed with NIFTP vs papillary and follicular thyroid cancer.

Results

NIFTP comprised 2.2% and 2.6% of cases in 2018 and 2019, respectively. Between 2018 and 2019, large heterogeneity was observed in the regional use of NIFTP diagnosis, with site-specific incidence rates between 0.0% and 6.2% (median 2.8%, interquartile range 1.3-3.6%). A diagnosis of NIFTP (vs papillary and follicular thyroid cancer) in 2018 and 2019 was significantly associated with older age (P = 0.012 and P = 0.009, respectively), Black race (both Ps < 0.001), and non-Hispanic ethnicity (both Ps < 0.001).

Conclusions

Marked variation exists in the use of the NIFTP diagnosis. The recent 2021 coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis to SEER will disproportionately affect vulnerable patient groups such as older patients and Black patients, in addition to patients who reside in regions with higher rates of NIFTP diagnoses.
Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
Authors: Kobayashi Tomoko , Iwama Shintaro , Yamagami Ayana , Yasuda Yoshinori , Okuji Takayuki , Ito Masaaki , Zhou Xin , Ando Masahiko , Onoue Takeshi , Miyata Takashi , Sugiyama Mariko , Hagiwara Daisuke , Suga Hidetaka , Banno Ryoichi , Hase Tetsunari , Morise Masahiro , Ito Takanori , Kikumori Toyone , Inoue Megumi , Ando Yuichi , Masuda Norikazu , Kawashima Hiroki , Hashimoto Naozumi , Arima Hiroshi
Published: August 2022

Background

Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients.

Methods

A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped.

Results

Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592–45.115), respectively.

Conclusion

The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs.
The Bupivacaine Story: A Tribute to George A. Albright, MD (1931–2020)
Authors: Larson C. Philip , Youssefzadeh Kevin , Moon Jane S.
Published: August 2022

In 1979, George A. Albright, MD (1931–2020) published a controversial editorial in Anesthesiology that raised the question of bupivacaine cardiotoxicity. In it, he presented several cases of rapid cardiovascular collapse after administration of the highly lipophilic local anesthetic and called for further investigation. Although the scientific community initially resisted Dr Albright’s idea, his editorial would ultimately lead to several important advancements in anesthesiology. In 1983, the US Food and Drug Administration issued a black box warning that recommended against the use of 0.75% bupivacaine in obstetric anesthesia. This warning would remain in place until 1999. In addition, Dr Albright’s article led to the following changes: laboratory research that proved the cardiotoxicity of bupivacaine; the development of safer, stereoselective agents like ropivacaine; and the acceptance of lipid emulsion as a treatment for local anesthetic toxicity. In this article, C. Philip Larson, Jr, MDCM, Editor-in-Chief of Anesthesiology at the time of publication of Albright’s manuscript, provides a unique perspective on the bupivacaine story.
Black Futures Not Yet Lost
Authors: Perry Kennetta Hammond
Published: August 2022

This essay explores how the resurgence of the Black Lives Matter movement’s public visibility during the summer of 2020 opened critical space to reconsider and critique entrenched narratives of British abolitionism that render the fate of post-emancipation Black futures inconsequential. It highlights some of the contestations within a British historiographical tradition that has co-opted abolitionism as a means to engender and fortify mythologies of a liberal and progressive white nation to the detriment of even conceiving of Black freedom as a requisite to emancipation. Black political thinkers from the period of enslavement to the present have continually spoken back to these abridged and romanticized histories of British abolitionism calling into view the limits of white abolitionist projects. This article outlines some of the intellectual currents that have shaped a history of Black abolitionist praxis in Britain as a political posture rooted in an acknowledgment of abolition’s unfinished work and its import in the present in anticipation of free Black futures yet to come.
A comparative study on the efficacy of robot of stereotactic assistant and frame-assisted stereotactic drilling, drainage for intracerebral hematoma in patients with hypertensive intracerebral hemorrhage
Authors: Liang Liang , Li Xin , Dong Haiqing , Gong Xin , Wang Guanpeng
Published: August 2022

Objectives: To compare the clinical efficacy of robot of stereotactic assistant (ROSA) and frame-assisted stereotactic drilling and drainage for intracerebral hematoma in hypertensive intracerebral hemorrhage (HICH).

Methods: A total of 142 patients with HICH treated in Baoding First Central Hospital from January 2018 to January 2020 were selected and divided into two groups using a random number table. The ROSA group was treated with a robot of stereotactic assistant, while the frame group underwent frame-assisted stereotactic drilling and drainage for intracerebral hematoma. Surgical duration, postoperative extubation time and complications were compared between the two groups. Venous blood (5 mL) was collected before and three days after surgery. The levels of inflammatory factors [tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6)], as well as neurological function indexes [neuron-specific enolase (NSE), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)] were detected by enzyme-linked immunosorbent assay.

Results: The surgical duration, postoperative extubation time, and incidences of infection and postoperative rehemorrhage in the ROSA group were lower than those in the frame group (P < 0.05). In the ROSA group, postoperative TNF-α, hs-CRP, IL-6 and NSE levels were significantly lower while NGF and BDNF levels were higher than those in the frame group (all P < 0.05).

Conclusion: Compared with frame-assisted stereotactic drilling and drainage for intracerebral hematoma, ROSA in HICH treatment shortens the surgical duration and postoperative extubation time, reduces the risks of infection and rehemorrhage and decreases inflammatory level, which is helpful for the recovery of neurological function.

doi: https://doi.org/10.12669/pjms.38.7.5481

How to cite this:Liang L, Li X, Dong H, Gong X, Wang G. A comparative study on the efficacy of robot of stereotactic assistant and frame-assisted stereotactic drilling, drainage for intracerebral hematoma in patients with hypertensive intracerebral hemorrhage. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5481

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comparison of PAP smear and liquid based cytology as a screening method for cervical carcinoma
Authors: Khakwani Mehnaz , Parveen Rashida , Azhar Maryam
Published: August 2022

Objectives: To compare conventional PAP smear (CPS) and liquid-based cytology (LBC) for cervical carcinoma screening at a tertiary care hospital of South Punjab, Pakistan.

Methods: This cross-sectional study was conducted at the Department of Obstetrics and Gynecology, Nishtar Hospital, Multan, Pakistan from January 2021 to June 2021. We included a total of 265 women aged between 20 to 65 years who, presented with complaints related to cervical lesion and unhealthy cervix. The CPS and LBC methods were applied for screening of cervical carcinoma. Findings of both CPS and LBC were compared with histopathological findings to find out sensitivity, specificity, positive predictive value and negative predictive value for both techniques.

Results: In a total of 265 women, mean age was noted to be 45.4±6.8 years. White discharge per vagina was the commonest presenting complaint noted in 12 (46.8%) patients. Satisfactory smears were found in significantly more cases with LBC in comparison to CPS (p<0.001). Sensitivity CPS and LBC for the detection of low-grade squamous intraepithelial lesion (LSIL) were found to be 71.8% and 87.2% while for high-grade squamous intraepithelial lesion (HSIL), sensitivity of CPS and LBC were 61.9% and 76.2% respectively. Specificity of CPS and LBC for the detection of LSIL was found to be 97.9% and 98.7% while for HSIL, specificity of CPS and LBC was 98.7% and 99.2% respectively.

Conclusion: In comparison to conventional CPS, LBC was found to be better in terms of adequacy of smear and identification of LSIL and HSIL.

doi: https://doi.org/10.12669/pjms.38.7.5742

How to cite this:Khakwani M, Parveen R, Azhar M. Comparison of PAP smear and liquid based cytology as a screening method for cervical carcinoma. Pak J Med Sci. 2022;38(7):---------. doi: https://doi.org/10.12669/pjms.38.7.5742

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Adverse COVID-19 vaccination effects in Finnish patients with Ménière’s disease: a cross-sectional study
Authors: Beukes Eldre , Manchaiah Vinaya , Pyykkö Nora , Pyykkö Ilmari
Published: August 2022

Background: The association between reporting adverse coronavirus disease 2019 (COVID-19) vaccination effects and those with a history of audiovestibular difficulties is unknown. The aim of this research is therefore to investigate adverse vaccination effects in adults with a history of Ménière’s disease. Specifically, the incidence of adverse effects, the factors associated with those reporting adverse effects and the relationship between the reporting of audiovestibular and other adverse effects.

Methods: A mixed-methods exploratory cross-sectional survey study design was used. Data were collected from 333 members of the Finnish Ménière Association. The survey was designed to obtain demographic information that may be associated with having adverse effects or not, vaccination-specific information and adverse vaccination effects. Both health and audiovestibular adverse events were identified. Data analysis included comparing those reporting and not reporting adverse vaccination effects.

Results: The mean age was 63 years with 81% being female. Of the 327 respondents who had one of the COVID-19 vaccinations (Comirnatry/ Pfizer, Astra Zeneca, or Moderna), 203 (62%) reported no adverse effects. The type of or number of vaccinations were not related to the reporting of adverse effects. The most frequently reported adverse effects were injection site tenderness (38%), arm pain (21%), fever (15%) and headaches (15%). Post-vaccination tinnitus and vertigo (both 7%) were the most frequently reported audiovestibular-related symptoms, followed by aural fullness (6%) and hearing loss (4%). Those reporting previous pre-vaccination vertigo were more likely to have post-vaccination vertigo. The presence of post-vaccination tinnitus, hearing loss, and aural fullness, predicted the presence of post-vaccination vertigo.

Conclusions: A small proportion of patients with a history of Ménière’s disease may experience adverse post-vaccination effects. Further research is required to explore whether adverse post-vaccination audiovestibular effects are more prevalent in those with a history of otological disorders compared with the general population.
Next-generation sequencing (NGS) reveals low-abundance HIV-1 drug resistance mutations among patients experiencing virological failure at the time of therapy switching in Uganda
Authors: Namaganda Maria Magdalene , Sendagire Hakim , Kateete David Patrick , Kigozi Edgar , Luutu Nsubuga Moses , Ashaba Katabazi Fred , Kabahita Jupiter Marina , Kakembo Fredrick Elishama , Kanyerezi Stephen , Castelnuovo Barbara , Kambugu Andrew , Ssewanyana Isaac , Okirya Chris , Nabadda Susan , Joloba Moses , Mboowa Gerald
Published: August 2022

Background: The emergence and spread of antiretroviral drug resistant HIV-1 variants is one of the major factors associated with therapeutic failure in persons living with HIV (PLWH) as it jeopardizes the efforts to reduce the progression to AIDS. Whereas Sanger sequencing is the most appropriate conventional method for HIV drug resistance testing, it has limited capacity to detect low-abundance variants. This study assessed the suitability of next generation sequencing (NGS) to reveal low-abundance HIV-1 drug resistance mutations amongst patients experiencing virological failure at the time of therapy switching in Uganda.

Methods: Archived blood samples previously collected from 60 PLWH were used in this study. Briefly HIV viral RNA was extracted and performed targeted NGS of portions of both the HIV protease and reverse transcriptase genes on the illumina MiSeq. For performance comparison, Sanger sequencing was also performed for all the samples targeting the highlighted genes. The sequence data generated was analyzed using HyDRA bioinformatics pipeline, accompanied by the Stanford HIV drug resistance database, to annotate and report drug resistance mutations/variants.

Results: Out of the 60 samples, 58 passed preliminary quality control and were considered for subsequent analysis—of which 38/58 (65.5%) registered low-abundance HIV drug resistance variants. Overall, 757 variants from the NGS data and 90 variants from the Sanger data were identified. The most prevalent minority variants included; K65R (65.5%), K14R (63.8%), K45R (63.8%), L63P (63.8%), I15V (63.8%), K70R (60.3%), V77I (60.3%), L283I (60.3%), G16E (58.6%) and L282C (58.6%).

Conclusion: An estimated 65.5% of the sampled population harbors low-abundance HIV-1 variants, most of which are associated with virological failure, and consequently antiviral drug resistance. NGS suitably detects drug resistance mutations even at frequencies below 20% of the viral quasi species that are occasionally missed by Sanger sequencing.
The effect of ingestion of red dragon fruit extract on levels of malondialdehyde and superoxide dismutase after strenuous exercise in rats (Rattus norvegicus)
Authors: Rusip Gusbakti , Ilyas Syafrudin , Lister I. Nyoman Ehrich , Ginting Chrismis N. , Mukti Indra
Published: August 2022

Background: Prolonged activation of skeletal muscles causes a decrease in the production of fatigue. Exercise with strenuous intensity causes an increase in Reactive Oxygen Species (ROS). An increase in free radicals causes oxidative stress resulting in damage to cell function to mitochondrial dysfunction, and fatigue. This study aimed to determine the antioxidant potential of red dragon fruit (RDF) to delay fatigue due to oxidative stress, which improves cell function in mitochondria.

Methods: 25 male rats (Rattus norvegicus) aged three months were divided into five groups: Group K1 was N.A. (No Activity) but drinking and eating; Group K2 performed strenuous exercise without RDF treatment; Groups 3, 4, and 5 (P1, P2 and P3, respectively) performed strenuous exercise and were treated with 75 mg kg-1.bw, 150 mg kg-1.bw, and 300 mg kg-1.bw of RDF extract, respectively. The exercise for the rats involved intense swimming for 20 minutes  a day three time a week for fouweeks.  Malondialdehyde (MDA) dan SOD was measured with the ELISA and histopathology for muscle soleus and lung tissue.

Results: Strenuous exercise followed by RDF extract ingestion was compared for fatigue in terms of duration and time; before (24.55±1.38 minute) and after (95.31±7.82 minute) and led to a significant difference of 39% (p<0.01). The study also compared MDA before and after RDF extract ingestion in the K2 vs. the P1 group (p<0.05). At the same time, P2 differed more significantly (p<0.01). This indicated a spread of free radicals and featured histopathological damage of muscle cells. However, ingestion of RDF extract leads to improvement of soleus muscle cells; thus, repairs cell function, delaying fatigue.

Conclusion: This study confirmed that strenuous exercise, which causes an increase in ROS, intensifies free radicals with RDF extract ingestion and declines oxidative stress, repairing cell function and delaying fatigue.
Physico-chemical properties of waste derived biochar from community scale faecal sludge treatment plants
Authors: Nicholas Hannah Larissa , Mabbett Ian , Apsey Henry , Robertson Iain
Published: August 2022

Background: The dumping of untreated faecal sludge from non-sewered onsite sanitation facilities causes environmental pollution and exacerbates poor public health outcomes across developing nations. Long-term mechanisms to treat faecal sludge generated from these facilities are needed to resolve the global sanitation crisis and realize the Sustainable Development Goal (SDG) 6 “ensure availability and sustainable management of water and sanitation for all” by 2030.  Pyrolysis of faecal sludge removes pathogens and generates biochar, which can be used as a soil enhancer.

Methods: The properties of faecal sludge biochars from three full-scale treatment plants in India were determined via Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive x-ray (EDX) spectroscopy, crystal x-ray diffraction (XRD), proximate analyses, and BET surface area porosimetry.

Results:  Results showed that all three biochars had low specific surface area, high alkaline pH values, high ash content, and negative surface charge. Fourier transform infrared spectra showed the same surface functional groups present in each biochar. X-ray diffraction analysis showed the mineral composition of each biochar differed slightly. Scanning electron microscopy analysis indicated a porous structure of each biochar with ash particles evident.

Conclusions: Slight differences in the ash content, surface area, pH and mineral content was observed between the three biochars.
LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis
Authors: Lacey Charles , Musa Ahmed , Khalil El Tahir , Younis Brima , Osman Mohamed , Wiggins Rebecca , Keding Ada , Kaye Paul
Published: August 2022

Background: The leishmaniases are neglected tropical diseases caused by various Leishmania parasite species transmitted by sand flies. They comprise a number of systemic and cutaneous syndromes including kala-azar (visceral leishmaniasis, VL), cutaneous leishmaniasis (CL), and post-kala-azar dermal leishmaniasis (PKDL). The leishmaniases cause significant mortality (estimated 20 - 50,000 deaths annually), morbidity, psychological sequelae, and healthcare and societal costs. Treatment modalities remain difficult. E.g., East African PKDL requires 20 days of intravenous therapy, and frequently relapsing VL is seen in the setting of HIV and immunodeficiency. We developed a new therapeutic vaccine, ChAd63-KH for VL / CL / PKDL and showed it to be safe and immunogenic in a phase 1 trial in the UK, and in a phase 2a trial in PKDL patients in Sudan.   

Methods: This is a randomised double-blind placebo-controlled phase 2b trial to assess the therapeutic efficacy and safety of ChAd63-KH in patients with persistent PKDL in Sudan. 100 participants will be randomly assigned 1:1 to receive placebo or ChAd63-KH (7.5 x1010vp i.m.) at a single time point. Follow up is for 120 days after dosing and we will compare the clinical evolution of PKDL, as well as the humoral and cellular immune responses between the two arms.

Discussion: Successful development of a therapeutic vaccine for leishmaniasis would have wide-ranging direct and indirect healthcare benefits that could be realized rapidly. For PKDL patients, an effective therapeutic vaccination used alone   would have very significant clinical value, reducing the need for extensive hospitalization and chemotherapy. Combining vaccine with drug (immuno-chemotherapy) might significantly increase the effective life of new drugs, with lower dose / abbreviated regimens helping to limit the emergence of drug resistance. If therapeutic benefit of ChAd63-KH can be shown in PKDL further evaluation of the vaccine in other forms of leishmaniasis should be considered.

Clinicaltrials.gov registration: NCT03969134.
Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales – analysis of the Virus Watch household community cohort study
Authors: Hoskins Susan , Beale Sarah , Nguyen Vincent , Fragaszy Ellen , Navaratnam Annalan M.D. , Smith Colette , French Clare , Kovar Jana , Byrne Thomas , Fong Wing Lam Erica , Geismar Cyril , Patel Parth , Yavlinksy Alexei , Johnson Anne M. , Aldridge Robert W. , Hayward Andrew ,   Virus Watch Collaborative
Published: August 2022

Background: “Lockdowns” to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics. 

Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic’s second wave.

Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 – 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 – 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 – 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection.

Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.
A systematic review protocol for identifying the effectiveness of greenhouse gas mitigation interventions for health care systems in low- and middle-income countries
Authors: Blom Iris Martine , Asfura Javier Shafick , Eissa Mohamed , Mattijsen Juliette Claudine , Sana Hamaiyal , Haines Andrew , Whitmee Sarah
Published: August 2022

Background: Climate change is predicted to be our century's most significant health threat. In 2021, 46 countries committed to environmentally sustainable low carbon health care systems. Of those, 34 were from low- and middle-income countries (LMICs).  Currently, health systems are responsible for 4.4% of global greenhouse gas (GHG) emissions, with health systems in high-income countries (HICs) contributing the largest proportion to the sector's GHG emissions. However, future increases are predicted in LMICs in the absence of robust GHG mitigation. This systematic review aims to identify evidence-based GHG mitigation interventions to guide the transformation of health care systems towards net zero, specifically in LMICs. Additionally, potential synergies between interventions that aid adaption to climate change and mitigate GHG emissions will be investigated.

Methods: This protocol will follow the 'Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist of recommended items to address in a systematic review protocol'. A comprehensive search will be conducted on electronic databases identified as relevant. Search terms were identified to capture all relevant peer-reviewed, primary research published between 1990 and 2022. The risk of bias will be assessed, and the quality of evidence graded. The eventual narrative synthesis will feed into a theory of change framework on GHG mitigation of health care systems in LMICs.

Discussion: This systematic review will synthesise the existing evidence around GHG mitigation interventions across all scopes of emissions, including scope 1 (health care operations), scope 2 (energy), and scope 3 (supply chains). It can be used to inform recommendations on how health care systems in LMICs can reduce emissions while prioritising which actions to take to gain the most significant reductions in GHG emissions, considering ease of implementation, scope and cost. Finally, this can catalyse further research in this area which is urgently needed.
M.M. Speransky: features of Russian reforms
Authors: Matyuhin A.
Published: August 2022

The purpose of this article is to analyze the significance and political role of M.M. Speransky as the first theorist and methodologist of Russian reforms based on a rational, scientific approach, with a focus on identifying the civilizational, mental and political specifics of Russia. The article used such methods as historical, comparative and hermeneutic. Speransky was the founder of a special conservative-liberal trend in Russia, according to which, when carrying out any reforms, it is necessary to take into account the stable monarchical, autocratic traditions of public consciousness. He considered optimal the option of "reforms from above" controlled by the supreme power and the state apparatus, with the preservation of guarantees of stability and legality of socio-political processes. Historically, the institutions of the autocratic system were considered by Speransky not as "political rudiments", but as effective "levers" and "mechanisms" for carrying out the necessary transformations. According to Speransky, the reform strategy should include an in-depth analysis of well-thought-out preparatory measures and rational consistency of all elements of the reform program. Social transformations should be cautious, gradual, step-by-step, excluding any drastic, radical steps and measures. At the same time, the most important factors were both the enlightened nature of the state power itself, and the purposeful processes of public education, political education initiated by the authorities, and the formation of a mature legal consciousness in society in the direction of the development of civil society. The conservative-liberal path of reforms under the leadership of the supreme power was opposed by M.M. Speranian revolutionary and radical-liberal methods of socio-political transformations, which have destructive, destructive consequences for the country.
Measures of State support for employment in Latvia, Lithuania and Estonia
Authors: Alekseev Roman , Dyudyun Tatyana , Ezhov D.
Published: August 2022

According to the EU Eurostat data, for a long period of time, the Baltic countries have been leading the list of countries with high unemployment. During the COVID-19 pandemic, these indicators have become critical in their scale, so the national governments of these countries, with the help of the EU, are trying to change the situation for the better with the help of various measures of state support in the field of employment, stabilize these indicators and bring them to the level of pre-crisis 2019. The purpose of the study is a comprehensive analysis of state support measures of the Governments of Latvia, Lithuania and Estonia aimed at providing employment and combating unemployment as one of the factors affecting their socio-economic development. The methodology of the study includes a method of statistical analysis, with the help of which statistical data on the number of unemployed citizens in these countries (for the period 2014-2021) are compared, the dynamics of the population in the period under review is considered. Along with the statistical method, a SWOT analysis was used, on the basis of which the strengths and weaknesses of state support measures of the governments of the Baltic countries in order to support employment, potential threats from their application and new opportunities for supporting unemployed persons were identified. The authors of the study made proposals on the need for structural reforms aimed at improving the labor market in the Baltic states, such as: retraining citizens who lost their jobs during the pandemic, for state account, the introduction of stricter quotas for the entry of citizens from the territory of the former Soviet Union and obtaining a work visa, the provision of additional subsidies to small and medium-sized businesses, the release of their from paying taxes for the period of emerging pandemics.
Postoperative edema management with external compression for successful treatment of shredder injuries of the hand: a report of two cases
Authors: Ko Jun Gul , Jang Uk , Lee Jun Yong
Published: August 2022

Shredder injuries have a poor prognosis and are a problematic type of hand trauma. The authors describe the successful management of two cases of shredder injuries, one involving a child and the other involving an adult. In the child, the authors performed loose skin sutures for closure in the initial surgery and adjusted the degree of intensity of the external compression daily. According to the degree of tissue swelling, the skin sutures were gradually tightened. In the adult, the authors used external compression rather than sutures and adjusted the degree of intensity every day. When treating a shredder injury, the most crucial task is balancing perfusion and tissue pressure to reduce edema while preserving viability, thereby healing and restoring the original function and shape of the injured body part. This paper suggests that external compression may be an important postoperative edema management method in patients with hand shredder injuries.
A LEI 10.639/03 E PERSPECTIVA DO ENSINO DE LITERATURAS AFRICANAS E AFRO-BRASILEIRA: RUMO A UMA EDUCAÇÃO ANTIRRACISTA / Law 10.639/03 and perspective of teaching african and afro-brazilian literatures: towards an anti-racist education
Authors: Berte Simone De Barros , Maquêa Vera
Published: August 2022

Neste artigo, apresentamos uma reflexão sobre a implantação da Lei 10.639/2003 e o ensino de literatura africanas e afro-brasileira como parte de resultados do trabalho desenvolvido no PROFLetras da UNEMAT- Universidade do Estado de Mato Grosso, em Cáceres. Este artigo teve por objetivo refletir aspectos relativos à implementação do disposto na Lei nos currículos escolares, discutindo a educação antirracista que vai ao encontro da valorização das culturas dos povos africanos e afrodescendentes. Inicialmente, professoras e professores da rede pública de ensino de Mato Grosso apontaram, por meio de um formulário eletrônico, a situação do desenvolvimento da Lei 10.639/2003 atualmente, o que permitiu analisar seus contornos atuais após quase duas décadas de sua publicação. Na sequência, utilizamos as respostas obtidas para analisar e subsidiar nossa abordagem sobre a aplicabilidade da implementação da Lei, suas lacunas e avanços na visão desses profissionais da Educação Básica, bem como refletir acerca de possibilidades para se ampliar o alcance do proposto pela Preceito Legal por meio do ensino de literaturas africanas e afro-brasileira como uma possibilidade para trabalhar na perspectiva da educação antirracista. Para tanto, como aporte teórico apoiamos a pesquisa em Candido (2008), Assis Duarte (2008, 2017), Fanon (1968, 2008), Petit (2009), Petrônio (2007), Souza (1983), entre outros.
Medical cannabis in multiple sclerosis
Authors: Erridge Simon , Sodergren Mikael H , Weatherall Mark W
Published: August 2022

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects over 100 000 individuals in the UK. The symptoms of MS are heterogenous and correspond to the location of demyelination. However, common symptoms include sensory, motor, cognitive and affective disturbances. While the cornerstone of medical therapy is disease modifying agents, there is an ongoing need to develop symptomatic treatments. Cannabis-based medicinal products (CBMPs), which were partially legalised in the UK in November 2018, have been touted as a potential management option for the associated sequelae of MS. Nabiximols, an oromucosal spray containing cannabidiol and (−)-trans-Δ9-tetrahydrocannabinol, has been extensively evaluated for the treatment of MS-related spasticity. However, unlicensed CBMP formulations are a novel therapeutic class of medications, of which the clinical effects are less well known. Yet, there are promising indications for the use of CBMP in the symptomatic treatment of MS. This article reviews the literature on efficacy and safety of medical cannabis for people with MS.
Flea beetles of the West Indies: Subtribe Oedionychina Chapuis 1875, key to genera, new combinations, synonymy, checklist, and description of new genera and species (Coleoptera, Chrysomelidae, Galerucinae, Alticini)
Authors: KONSTANTINOV ALEXANDER S. , ROIE MARTIJN VAN , FURTH DAVID , CLARK SHAWN M. , RILEY EDWARD G.
Published: August 2022

West Indian genera of the flea beetle subtribe Oedionychina Chapuis, 1875 are reviewed. Two new genera and one new species are described: Argusonychis Konstantinov, Van Roie, & Furth gen. nov. with Argusonychis clarki Konstantinov, Van Roie & Furth sp. nov. as the type species (Bahamas); and Ciguapanychis Konstantinov, Van Roie & Furth gen. nov. with Alagoasa bicolor (Linnaeus, 1767) as the type species (Puerto Rico). An illustrated key to the genera found in the West Indies is provided. Each genus is illustrated with images of external and internal morphology, including thoracic structures, metendosternite, and female and male genitalia. Asphaera subfasciata Clark, 1860 is designated as the type species for Asphaera Duponchel & Chevrolat in d’Orbigny, 1842. The genus Ptena Chevrolat, 1836 is considered a long-overlooked senior synonym of Asphaera; the use of Asphaera is maintained. The lectotypes are designated for: Chrysomela albicollis Fabricius, 1787, Oedionychis crucipennis Suffrian, 1868, and Haltica decipiens Klug, 1829. Pleurasphaera Bechyné, 1958 is recognized as an objective junior synonym of Litosonycha Chevrolat, 1836 since these two generic names share the same type species, Haltica decipiens Klug, 1829. Oedionychis punctipennis Blake, 1971 is synonymized with Alagoasa sharpi (Jacoby, 1897). The following 17 new combinations are proposed: Alagoasa lunata (Fabricius, 1801), Alagoasa sharpi (Jacoby, 1897), Alagoasa smithi (Jacoby, 1897), Argusonychis megalopia (Blake, 1939), Argusonychis orientensis (Blake, 1959), Argusonychis zayasi (Blake, 1959), Asphaera amplilimbata (Blake, 1959), Asphaera cristalensis (Blake, 1959), Ciguapanychis bicolor (Linnaeus, 1767), Ciguapanychis dimidiatus (Olivier, 1808), Ciguapanychis fasciatus (Fabricius, 1798), Ciguapanychis jamaicensis (Jacoby, 1894), Ciguapanychis pseudofasciatus (Blake, 1940), Ciguapanychis viridipennis (Blake, 1971), Kuschelina pseudothoracica (Blake, 1945), Omophoita turquino (Zayas, 1988), and Walterianella gurneyi (Blake, 1968). The following three species are removed from synonymy and restored to species status as new combinations: Ciguapanychis cinctus (Olivier, 1808), Ciguapanychis lantanus (Blake, 1928), and Ciguapanychis purpurellus (Blake, 1940).
Analysis of a Stochastic Model with Rework System
Authors: Ram Mangey , Negi Ganga , Goyal Nupur , Kumar Anuj
Published: August 2022

The demand in the present global industrial system, requires the challenge to meet the growing consumer capabilities and requirements constantly. So, there is always a need to improve different parameters, one of them being different types of failures involved in the working of different engineering systems related to communication systems, manufacturing goods, nuclear and hydro power plants, automobiles and many others. Human error occurring in the working of various systems has always been the challenge to the researchers and is being constantly worked upon by the researchers in the analysis and improvement of reliability and availability of different complex and multistate systems. In the present paper, there is a three-unit system consisting of the unit A with two subunits in parallel and other units B and C are connected in series with A. The authors have investigated and analysed different reliability measures like availability, MTTF and sensitivity taking into account the human failure and carrying out rework system. This research work aims at the study of reliability and availability measures of a multi-state system incorporating human error so as to increase the efficiency of industrial systems by taking maintenance and rework measures to enhance the availability factors. This would help to understand and estimate the reliability measures of any such systems in the field of telecommunication, any electronic devices like that in small power plants, robot systems and such others. Also, a comparison has been made between the availability and reliability estimates in the presence and in the absence of human error. The techniques used are Markov process, Laplace transformation and supplementary variable technique.
Detection method of springback for linear guideway straightening using digital image correlation
Authors: Ling He , Yao Xuzhao , Lu Hong , Zhang Yongquan , Wang Zihao , Qin Yaoqing
Published: August 2022

The guideway deformation control of the straightening process is the basic method to ensure straightening accuracy. The prediction of and compensation for springback in the straightening process of a guideway adopts mostly numerical analysis and finite element analysis methods instead of experimental methods because of the measuring difficulty of actual springback. In this paper, a method is proposed to detect bending deformation during the straightening process, which provides a reference for the relevant manufacturing processes. Digital image correlation measurement technology is adopted for the detection of bending springback, which can measure the full-field displacement distribution without contact and with high precision. The experimental results show that digital image related technology can very accurately detect the deformation of the guideway straightening stroke and bending springback deformation. This study can help to control bending deformation during the straightening process and ensure straightening accuracy, providing a reference for real-time monitoring of straightening force.
Combined influence of the gain and dispersion of a mode-locked fiber laser on a time-stretching analog-to-digital conversion link
Authors: Chen Bowen , Wei Zihan , Zhao Ranyou , Xiao Lin , Deng Gang , Ma Wanzhuo , Wang Tianshu
Published: August 2022

Using theory and experiments, we demonstrated the combined influence of the spectral gain and dispersion of a dissipative soliton mode-locked fiber laser on a time-stretching analog-to-digital conversion link without an optical amplifier. The theoretical and experimental results indicate the following: first, the amplitude and envelope shape of the stretched signal are mainly affected by the spectral gain of the dissipative soliton at different central wavelengths under a radio frequency signal of 10 GHz. Second, at the higher frequency of 25 GHz, the influence of the phase shift induced by the dispersion of different spectral ranges on the amplitude of the stretched signal becomes clearer. The amplitude of the stretched signal across all spectral ranges decrease, and the envelope shape differs from that at 10 GHz. Moreover, the wavelength at the maximum amplitude of the stretched signal changes, for which the influence of the spectral dispersion is greater than that of the spectral gain. Finally, the ratio of the amplitude at 25 GHz to that at 10 GHz at different spectral ranges are different, which indicates that the amplitude of the stretched signal at different spectral ranges is affected by the phase shift by different degrees.
Adjustment on the received optical power of a ground-based optical instrument by a corner cube retroreflector with a curved front-face: publisher’s note
Authors: Hui Zhou , Song Li , Chen Yuwei
Published: August 2022

This publisher’s note corrects errors in Appl. Opt.
60, 405 (2021) APOPAI0003-693510.1364/AO.412481.