bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Clinical Pharmacy Surveillance on Pharmacy Services: A Quality Improvement Project
Authors: Kramer Joan S. , Borum Cynthia , Claxon Evan L. , Wines Kahari J. , Fraker Sarah , Burgess L. Hayley
Published: September 2023

Goal:

The purpose of this quality improvement project was to retrospectively evaluate pharmacist time to clinical surveillance alert intervention before and after implementing a pharmacy-directed alert priority category across a large for-profit United States health system with well-established clinical pharmacy surveillance software integrated into the clinical pharmacy workflow. The findings contributed to a financial evaluation of pharmacist productivity compared with drug spend for pharmacy-directed interventions that included intravenous (IV)-to-oral-conversion and renal dosing opportunities.

Methods:

A retrospective quality improvement pre-/postanalysis of deidentified, prepopulated clinical surveillance alert data for the preimplementation period of January 1, 2021, through September 30, 2021, was compared with that for the postimplementation period of November 1, 2021, to January 31, 2022, for 169 hospitals. Clinical pharmacist workflow was mapped pre- and postimplementation. The average time to alert intervention was calculated using the mean time in minutes between the alert firing within the software and when the pharmacist reviewed the alert, grouped by hospital, alert status, and priority category. Medications converted from IV to oral were assessed using the clinical surveillance software IV-to-oral calculator. Postimplementation renal dose cost savings were modeled using pharmacist-completed alerts by rule name that indicated a possible dose decrease based on the patient's renal function and current medication.

Principal Findings:

Time to alert intervention for all completed pharmacist interventions was reduced for high-priority alerts by 32.6 min (p < .001) and routine-priority alerts by 65.1 min (p = .147). Alerts that moved to the pharmacy-directed alert priority category resulted in a reduced time to alert intervention of 38.7 min (p = .003). Normalized average wholesale price (AWP) cost savings from IV-to-oral conversion within 3 days of conversion eligibility were $1,693,600 in the preimplementation period and $1,867,400 in the postimplementation period, a $173,700 increase in cost savings. A total of 7,972 completed postimplementation renal dose adjustments resulted in a modeled AWP normalized cost savings of $1,076,700.

Practical Applications:

Results indicated that optimizing clinical surveillance software alerts was effective and increased pharmacist productivity. Specifically, creating a pharmacy-directed alert category that pharmacists were able to complete by hospital policy or protocol improved workflow efficiency and increased IV-to-oral medication conversion cost savings. Further study is needed to validate the renal dose–modeled cost savings and address the financial benefits of quality measures to prevent acute kidney injury.
Bibliometric analysis and visualization of research trends in total mesorectal excision in the past twenty years
Authors: Pan Yun , Deng Xianyu , Chen Xin , Lin Moubin
Published: September 2023

Background:

Rectal cancer leads a major disease burden worldwide. Total mesorectal excision (TME) is the standard treatment for locally advanced or node-positive rectal cancer, while attempts to improve the surgery such as laparoscopic and transanal TME are widely used but have their inherent limitations. This bibliometric study analyzed research trends, cooperation and knowledge dissemination on TME over the past 20 years to inform future directions.

Methods:

Relevant literature from 2003-2023 was extracted from Web of Science Core Collection and analyzed with VOSviewer, CiteSpace, and R for publication patterns, countries, institutions, authors, and research hotspots.

Results:

5,345 related publications were included, with rising annual output and citations. The US and China contributed the most studies, while the Netherlands had greater influence. Leiden University ranked first in publications. Top authors were Heald, Kapiteijn, Sauer, Nagtegaal, and Peeters. Researches shifted from cancer-focused to patient-centered care and from radiotherapy/chemotherapy to advanced surgery. Multicenter trials became more common.

Conclusion:

Although the United States and China have the largest number of publications, it should be noted that the influence of these two countries in the field of TME research is not the highest, which does not match the number of publications. In addition, telemedicine, interdisciplinary, medical-industrial integration, etc. may be potential directions for future research in the field of TME.
Long-term outcomes of mitral valve replacement in dialysis patients: evidence from a nationwide database
Authors: Yang Kelvin J. , Fu Hsun-Yi , Chang Chia-Jui , Wang Ting-Chuan , Wang Chih-Hsien , Chou Nai-Kuan , Wu I-Hui , Hsu Ron-Bin , Huang Shu-Chien , Yu Hsi-Yu , Chen Yih-Sharng , Chi Nai-Hsin
Published: September 2023

Background:

To compare the late outcomes between mechanical and bioprostheses after isolated mitral valve replacement (MVR) in dialysis-dependent patients.

Methods:

A nationwide propensity-matched retrospective cohort study was conducted involving dialysis patients who underwent primary mitral replacement between 2001 and 2018. Ten-year postoperative outcomes were compared between mitral bioprosthesis and mechanical prosthesis using the Cox proportional hazard model and restricted mean survival time (RMST).

Results:

The all-cause mortality was 20.8 and 13.0 events per 100 person-years, with a 10-year RMST of 7.40 and 7.31 years for bioprosthesis and mechanical prosthesis, respectively. Major bleeding was the most common adverse event for both bioprosthesis and mechanical prosthesis, with an incidence rate of 19.5 and 19.1 events per 100 person-years, respectively. The incidence of valve reoperation was higher among those who received bioprosthesis (0.55 events per 100 person-years). After 1:1 matching, the all-cause mortality was 15.45 and 14.54 events per 100 person-years for bioprosthesis and mechanical prosthesis, respectively. The RMST at 10 years was comparable between the two groups after matching (5.10 years for bioprosthesis vs. 4.59 years for mechanical prosthesis), with an RMST difference of −0.03. Further, no difference was observed in the incidence of major adverse valve-related events between bioprosthesis and mechanical valves. However, bioprosthesis was associated with a higher incidence of mitral valve reoperation among all major adverse events (RMST difference −0.24 years, 95% CI −0.48 to −0.01, P=0.047).

Conclusions:

This study found no association between valve selection and long-term survival outcomes in dialysis patients after MVR. However, bioprosthetic valves may be associated with a slightly higher incidence of reoperation, while other valve-related adverse events, including major bleeding and stroke, were comparable between the two types of prostheses.
Auxiliary use of ChatGPT in surgical diagnosis and treatment
Authors: AU Kahei , Yang Wah
Published: September 2023

ChatGPT can be used as an auxiliary tool in surgical diagnosis and treatment in several ways. One of the most incredible values of using ChatGPT is its ability to quickly process and handle large amounts of data and provide relatively accurate information to healthcare workers. Due to its high accuracy and ability to process big data, ChatGPT has been widely used in the healthcare industry for tasks such as assisting medical diagnosis, giving predictions of some diseases, and analyzing some medical cases. Surgical diagnosis and treatment can serve as an auxiliary tool to help healthcare professionals. Process large amounts of medical data, provide real-time guidance and feedback, and increase healthcare’s overall speed and quality. Although it has great acceptance, it still faces issues such as ethics, patient privacy, data security, law, trustworthiness, and accuracy. This study aimed to explore the auxiliary use of ChatGPT in surgical diagnosis and treatment.
Optimal tentative abdominal closure for open abdomen: a multicenter retrospective observational study (OPTITAC study)
Authors: Yamamoto Ryo , Kuramoto Shunsuke , Shimizu Masayuki , Shinozaki Hiroharu , Miyake Tasuku , Sadakari Yoshihiko , Sekine Kazuhiko , Kaneko Yasushi , Kurosaki Ryo , Koizumi Kiyoshi , Shibusawa Takayuki , Sakurai Yoshihiko , Wakahara Sota , Sasaki Junichi ,   for the OPTITAC study group
Published: September 2023

Background:

Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure.

Materials and Methods:

A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (<50, 50–100, or >100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics.

Results:

Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (>100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50–0.69), P=0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30–82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00–0.50)].

Conclusion:

High negative pressure (>100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.
Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study
Authors: Fu Zhibing , Zeng Jinrong , Zhu Liyong , Wang Guohui , Li Pengzhou , Li Weizheng , Song Zhi , Su Zhihong , Sun Xulong , Tang Haibo , Luo Ping , Tan Lina , Gao Lihua , Wang Dan , Yan Siyu , Zhou Lu , Tong Xiaoliao , Tang Zhen , Zhang Hanyi , Tan Wenbin , Lu Jianyun , Zhu Shaihong
Published: September 2023

Background:

Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals.

Methods:

The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n=178) or OB with AN (OB_AN, n=141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG.

Results:

OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels (P<0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery (P<0.01).

Conclusion:

The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.
Long-term survival after major trauma: a retrospective nationwide cohort study from the National Health Insurance Research Database
Authors: Kuo Ling-Wei , Wang Yu-Hsin , Wang Chia-Cheng , Huang Yu-Tung A. , Hsu Chih-Po , Tee Yu-San , Chen Szu-An , Liao Chien-An
Published: September 2023

Background:

Most trauma-related studies are focused on short-term survival and complications within the index admission, and the long-term outcomes beyond discharge are mainly unknown. The purpose of this study was to analyze the data from the National Health Insurance Research Database (NHIRD) and to assess the long-term survival of major trauma patients after being discharged from the index admission.

Material and Methods:

This retrospective, observational study included all patients with major trauma (injury severity score ≥16) in Taiwan from 2003 to 2007, and a 10-year follow-up was conducted on this cohort. Patients aged 18–70 who survived the index admission were enrolled. Patients who survived less than one year after discharge (short survival, SS) and those who survived for more than one year (long survival, LS) were compared. Variables, including preexisting factors, injury types, and short-term outcomes and complications, were analyzed, and the 10-year Kaplan–Meier survival analysis was conducted.

Results:

In our study, 9896 patients were included, with 2736 in the SS group and 7160 in the LS group. Age, sex, comorbidities, low income, cardiopulmonary resuscitation event, prolonged mechanical ventilation, prolonged ICU length of stay (LOS), and prolonged hospital LOS were identified as the independent risk factors of SS. The 10-year cumulative survival for major trauma patients was 63.71%, and the most mortality (27.64%) occurred within the first year after discharge.

Conclusion:

27.64% of patients would die one year after being discharged from major trauma. Major trauma patients who survived the index admission still had significantly worse long-term survival than the general population, but the curve flattened and resembled the general population after one year.
Supragastric belching and rumination syndrome: diagnosis and management
Authors: Davidson Kate , Sibley Haley , O’Rourke Ashli K.
Published: September 2023

Purpose of review

This review article aims to discuss the clinical presentation and diagnosis of rumination syndrome and supragastric belching, as well as treatment options for both diseases.

Recent findings

Functional gastrointestinal disorders such as rumination syndrome and supragastric belching may be effectively treated using biofeedback.

A comprehensive approach that includes potential pharmacologic treatments, cognitive behavioral therapy and biofeedback should also be considered for optimal management of supragastric belching and rumination.
How Does CLEFT-Q Change the Way We Practice? A Prospective Study Integrating Patient-Reported Outcomes
Authors: Salinero Lauren K. , Cheung Liana , Villavisanis Dillan F. , Wagner Connor S. , Barrero Carlos E. , Pontell Matthew E. , Jackson Oksana A. , Taylor Jesse A. , Low David W. , Swanson Jordan W.
Published: September 2023

Background:

The CLEFT-Q is a validated instrument designed to elicit patient-reported outcomes among people affected by cleft lip and/or palate. However, it has not been reported how use of CLEFT-Q data alters routine cleft care. This study analyzed the impact of CLEFT-Q data integration on patient care and clinical decision-making.

Methods:

Patients were sequentially, prospectively evaluated during scheduled cleft team visits. The CLEFT-Q was completed before the clinic encounter, but results were initially masked from the surgeon and family. In the encounter, a study observer characterized patients’ verbalized attitudes across 7 specific domains of appearance and function, and the provisional assessment and plan was noted. CLEFT-Q data were then introduced into the clinical encounter and discussed. Discordance between patients’ initially verbalized attitudes and their self-reported scores on the CLEFT-Q was documented along with any resultant modifications to their care plan.

Results:

Seventy patient visits were observed; the mean patient age was 12.7 years (range, 8 to 19 years). Forty-one patients (59%) had cleft lip and palate/alveolus and 29 (41%) had isolated cleft palate. Discordance was observed in 36% of visits and in 9.2% of specific domains assessed. Highest discordance rates were observed in domains of psychosocial function (12.5%), speech function/distress (11.6%), and lips/lip scar appearance (11.6%). No age group or sex was associated with increased discordance. Integration of CLEFT-Q results altered the assessment and plan in 11 visits (16%).

Conclusion:

The CLEFT-Q provides clinically relevant insight into patient perspectives that are not captured by routine interview and examination alone, and regularly leads to a change in the management plan.
Gearing Effect in Clockwise Rotational Orthognathic Surgery
Authors: Woo Soo Hyun , Kim Young Chul , Lee Jang Yeol , Choi Jong Woo
Published: September 2023

Background:

The standard procedure for managing skeletal class III malocclusion is maxillary advancement with mandibular setback. Occlusal plane–altering orthognathic surgery, such as jaw rotation, is useful as well. Although clockwise jaw rotation is a common procedure, its mechanism has not been well investigated. With this study, the authors aim to introduce the gearing effect to correct class III malocclusion in Asians by maxillary posterior impaction using clockwise rotation without advancing the maxilla.

Methods:

Patients with class III correction with clockwise rotation of the maxillomandibular complex without maxillary advancement were included; those who underwent genioplasty were excluded. Various facial skeletal cephalometric landmarks were measured using artificial intelligence–based cephalometric analysis software. The gearing effect was determined by dividing the lower anterior facial height (LAFH) in relatively short and long groups compared with those in the anterior nasal spine to posterior nasal spine length.

Results:

In a total of 29 patients, the amount of menton setback between group 1 (n = 15; short LAFH) and group 2 (n = 14; long LAFH) was 1.67 ± 0.66 and 2.74 ± 0.99 mm per 1 mm of posterior nasal spine impaction, respectively (P = 0.002), and 1.58 (interquartile range, 0.78) and 1.95 (interquartile range, 1.05) mm per 1 degree of clockwise rotation of the palatal angle, respectively (P = 0.007). The convexity of the A point was improved without any significant change in the sella-nasion–A point angle before and after surgery.

Conclusions:

This article addresses the scientific evidence regarding the impact of clockwise rotational orthognathic surgery based on the gearing effect. The mandibular setback turned out to be more effective in patients with a long LAFH.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Irradiation Affects Adipose-Derived Stem Cells and Wound Healing Depending on Radiation Dose and Frequency
Authors: Asahi Rintaro , Sunaga Ataru , Shirado Takako , Saito Natsumi , Mori Masanori , Yamamoto Yoshihiro , Wu Yunyan , Yoshimura Kotaro
Published: September 2023

Background:

Radiation therapies are often associated with permanent devitalization in the surrounding tissue. The authors hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function, including wound-healing capacity.

Methods:

Susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0 to 10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on mouse dorsal skin (n = 4 to 5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using 1 of 3 fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were measured periodically, and wound healing and tissue immunohistology were compared at 6 months.

Results:

A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the 3 in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (ie, skin dysfunction, subcutaneous atrophy, depletion of CD34+ stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group.

Conclusion:

These results have important clinical implications for surgeons and radiotherapists in the timing of surgical interventions and the optimization of fractionation protocols.

Clinical Relevance Statement:

Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, surgeons can minimize the long-term functional deficits of radiated tissue without losing the anticancer efficacy of radiation therapy.
Alteromonas gilva sp. nov. and Erythrobacter fulvus sp. nov., isolated from a tidal mudflat
Authors: Park Sunho , Kim Inhyup , Chhetri Geeta , So Yoonseop , Jung Yonghee , Woo Haejin , Seo Taegun
Published: September 2023

Strains chi3T and sf7T were collected from a tidal mudflat around Dongmak beach in Ganghwa, Republic of Korea. Both strains were Gram-stain-negative, aerobic or facultatively anaerobic, and rod-shaped. Results of phylogenetic tree analysis based on 16S rRNA and whole-genome sequences suggested that strains chi3T and sf7T belong to the genera

Alteromonas

and

Erythrobacter

, respectively. The cells of strain chi3T were non-motile and grew at 15–45 °C (optimum, 38 °C), at pH 6.0–10.0 (optimum, pH 8.0) and in the presence of 0–9.0 % (w/v) NaCl (optimum, 2.0 %). The cells of strain sf7T were motile as they had flagella and grew at 20–48 °C (optimum, 38 °C), at pH 6.0–10.0 (optimum, pH 9.0) and in the presence of 0–5.0 % (w/v) NaCl (optimum, 1.0 %). Strains chi3T and sf7T have average nucleotide identity values (70.0–70.4% and 78.9–81.7 %) and digital DNA–DNA hybridization values (21.8–22.3% and 21.0–25.6 %) with reference strains in the genera

Alteromonas

and

Erythrobacter

, respectively. Data from digital DNA–DNA hybridization, as well as phylogenetic, biochemical and physiological analyses, indicated the distinction of the two strains from the genera

Alteromonas

and

Erythrobacter

, respectively, and we thus propose the names Alteromonas gilva sp. nov. (type strain chi3T=KACC 22866T=TBRC 16612T) and Erythrobacter fulvus sp. nov. (type strain sf7T=KACC 22865T=TBRC 16611T).
RNase L-activating 2′–5′ oligoadenylates bind ABCF1, ABCF3 and Decr-1
Authors: Govande Apurva A. , Babnis Aleksandra W. , Urban Christian , Habjan Matthias , Hartmann Rune , Kranzusch Philip J. , Pichlmair Andreas
Published: September 2023

A notable signalling mechanism employed by mammalian innate immune signalling pathways uses nucleotide-based second messengers such as 2′3′-cGAMP and 2′–5′-oligoadenylates (OAs), which bind and activate STING and RNase L, respectively. Interestingly, the involvement of nucleotide second messengers to activate antiviral responses is evolutionarily conserved, as evidenced by the identification of an antiviral cGAMP-dependent pathway in Drosophila. Using a mass spectrometry approach, we identified several members of the ABCF family in human, mouse and Drosophila cell lysates as 2′–5′ OA-binding proteins, suggesting an evolutionarily conserved function. Biochemical characterization of these interactions demonstrates high-affinity binding of 2′–5′ OA to ABCF1, dependent on phosphorylated 2′–5′ OA and an intact Walker A/B motif of the ABC cassette of ABCF1. As further support for species-specific interactions with 2′–5′ OA, we additionally identified that the metabolic enzyme Decr1 from mouse, but not human or Drosophila cells, forms a high-affinity complex with 2′–5′ OA. A 1.4 Å co-crystal structure of the mouse Decr1–2′–5′ OA complex explains high-affinity recognition of 2′–5′ OA and the mechanism of species specificity. Despite clear evidence of physical interactions, we could not identify profound antiviral functions of ABCF1, ABCF3 or Decr1 or 2′–5′ OA-dependent regulation of cellular translation rates, as suggested by the engagement of ABCF proteins. Thus, although the biological consequences of the here identified interactions need to be further studied, our data suggest that 2′–5′ OA can serve as a signalling hub to distribute a signal to different recipient proteins.
Nifuroxazide Suppresses PD-L1 Expression and Enhances the Efficacy of Radiotherapy in Hepatocellular Carcinoma
Authors: Zhao Tiesuo , Wei Pengkun , Zhang Congli , Zhou Shijie , Liang Lirui , Guo Shuoshuo , Yin Zhinan , Cheng Sichang , Gan Zerui , Xia Yuanling , Zhang Yongxi , Guo Sheng , Zhong Jiateng , Yang Zishan , Tu Fei , Wang Qianqing , Bai Jin , Ren Feng , Feng Zhiwei , Jia Huijie
Published: September 2023

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosisin vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.
IMPACT OF THE COVID-19 PANDEMIC ON ROUTINE HIV CARE AND ANTIRETROVIRAL TREATMENT OUTCOMES IN KENYA: A NATIONALLY REPRESENTATIVE ANALYSIS
Authors: Kimanga Davies O. , Makory Valeria N.B. , Hassan Amin S. , Ngari Faith , Ndisha Margaret M. , Muthoka Kennedy J. , Odero Lydia , Omoro Gonza O. , Aoko Appolonia , Ng’ang’a Lucy
Published: September 2023

Background

The COVID-19 pandemic adversely disrupted global health service delivery. We aimed to assess impact of the pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and initial virologic non-suppression (VnS) among individuals starting antiretroviral therapy (ART) in Kenya.

Methods

Individual-level longitudinal service delivery data were analysed. Random sampling of individuals aged >15 years starting ART between April 2018 – March 2021 was done. Date of ART initiation was stratified into pre-COVID-19 (April 2018 – March 2019 and April 2019 – March 2020) and COVID-19 (April 2020 – March 2021) periods. Mixed effects generalised linear, survival and logistic regression models were used to determine the effect of COVID-19 pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and VnS, respectively.

Results

Of 7,046 individuals sampled, 35.5%, 36.0% and 28.4% started ART during April 2018 – March 2019, April 2019 – March 2020 and April 2020 – March 2021, respectively. Compared to the pre-COVID-19 period, the COVID-19 period had higher same-day HIV diagnosis/ART initiation (adjusted risk ratio [95% CI]: 1.09 [1.04–1.13], p<0.001) and lower six-months non-retention (adjusted hazard ratio [95% CI]: 0.66 [0.58–0.74], p<0.001). Of those sampled, 3,296 (46.8%) had a viral load test done at a median 6.2 (IQR, 5.3–7.3) months after ART initiation. Compared to the pre-COVID-19 period, there was no significant difference in VnS during the COVID-19 period (adjusted odds ratio [95% CI]: 0.79 [95%% CI: 0.52–1.20], p=0.264).

Conclusions

In the short term, the COVID-19 pandemic did not have an adverse impact on HIV care and treatment outcomes in Kenya. Timely, strategic and sustained COVID-19 response may have played a critical role in mitigating adverse effects of the pandemic and point towards maturity, versatility and resilience of the HIV program in Kenya. Continued monitoring to assess long-term impact of the COVID-19 pandemic on HIV care and treatment program in Kenya is warranted.
Abundance of Northern Hemisphere tree species declines in the warm and arid regions of their climatic niches
Authors: Astigarraga Julen , Esquivel-Muelbert Adriane , Ruiz-Benito Paloma , Rodríguez-Sánchez Francisco , Zavala Miguel A. , Vilà-Cabrera Albert , Schelhaas Mart-Jan , Kunstler Georges , Woodall Christopher W. , Cienciala Emil , Dahlgren Jonas , Govaere Leen , König Louis A. , Lehtonen Aleksi , Talarczyk Andrzej , Pugh Thomas A. M.
Published: September 2023

Climate change is expected to drive species towards colder and wetter regions of their distribution with alternative processes such as forest management having the potential to alter species displacements. Here, using data from more than two million monitored trees from 73 widely-distributed species, we quantify changes in tree species abundance across Northern Hemisphere forests and find a widespread decline in abundance across the whole of species’ climatic niches. Yet, our analysis revealed that this decline is heavily influenced by alterations at the stand-level and consequent stand development. Remarkably, when accounting for stand development, our findings show a consistent trend of species abundance optimum shifting towards cold and wet regions within their climatic niches. We provide species-specific information on the direction and magnitude of climate-driven changes in abundance that should be taken into account when designing conservation, management and restoration plans in an era of unprecedented human-caused environmental change.
Harmonized decay classification for dead wood in Nordic national forest inventories
Authors: Aakala Tuomas , Heikkinen Juha
Published: September 2023

Dead wood quality is recorded as a biodiversity indicator and in estimating forest ecosystem carbon storage, using decay classification systems. In large-scale national forest inventories (NFIs), these systems are typically slightly different among countries, but harmonizing them would allows analyses over much broader scales and the use of larger data sets. Here, we developed a harmonized decay classification for the NFIs of Finland, Norway, and Sweden, using wood density as the harmonizing criterion. We sampled 441 pine, spruce, birch and aspen in different conditions and decay classes, measured their density and developed the harmonized classification for each species and dead wood type (standing and fallen dead wood). The assignments relied on minimizing within-class variance in wood density in the harmonized classes. Assigned into three (standing dead wood) and four (fallen dead wood) classes, the harmonization led to some losses of information, especially in the advanced decay stages in Finnish and Norwegian classifications. Importantly, the harmonized classes included slightly different decay classes from the national classifications, depending on the tree species and type. This is an advantage over the expert assessment that typically treat all species and types of dead wood the same way despite clear differences in decomposition pathways.
Poor Generalization by Current Deep Learning Models for Predicting Binding Affinities of Kinase Inhibitors
Authors: Ong Wern Juin Gabriel , Kirubakaran Palani , Karanicolas John
Published: September 2023

The extreme surge of interest over the past decade surrounding the use of neural networks has inspired many groups to deploy them for predicting binding affinities of drug-like molecules to their receptors. A model that can accurately make such predictions has the potential to screen large chemical libraries and help streamline the drug discovery process. However, despite reports of models that accurately predict quantitative inhibition using protein kinase sequences and inhibitors’ SMILES strings, it is still unclear whether these models can generalize to previously unseen data. Here, we build a Convolutional Neural Network (CNN) analogous to those previously reported and evaluate the model over four datasets commonly used for inhibitor/kinase predictions. We find that the model performs comparably to those previously reported, provided that the individual data points are randomly split between the training set and the test set. However, model performance is dramatically deteriorated when all data for a given inhibitor is placed together in the same training/testing fold, implying that information leakage underlies the models’ performance. Through comparison to simple models in which the SMILES strings are tokenized, or in which test set predictions are simply copied from the closest training set data points, we demonstrate that there is essentially no generalization whatsoever in this model. In other words, the model has not learned anything about molecular interactions, and does not provide any benefit over much simpler and more transparent models. These observations strongly point to the need for richer structure-based encodings, to obtain useful prospective predictions of not-yet-synthesized candidate inhibitors.
Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer
Authors: Dannenfelser Ruth , Yao Vicky
Published: September 2023

Protein-protein interactions play an essential role in nearly all biological processes, and it has become increasingly clear that in order to better understand the fundamental processes that underlie disease, we must develop a strong understanding of both their context specificity (e.g., tissue-specificity) as well as their dynamic nature (e.g., how they respond to environmental changes). While network-based approaches have found much initial success in the application of protein-protein interactions (PPIs) towards systems-level explorations of biology, they often overlook the fact that large numbers of proteins undergo alternative splicing. Alternative splicing has not only been shown to diversify protein function through the generation of multiple protein isoforms, but also remodel PPIs and affect a wide range diseases, including cancer. Isoform-specific interactions are not well characterized, so we develop a computational approach that uses domain-domain interactions in concert with differential exon usage data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx). Using this approach, we can characterize PPIs likely disrupted or possibly even increased due to splicing events for individual TCGA cancer patient samples relative to a matched GTEx normal tissue background.
Harnessing Raman spectroscopy and Multimodal Imaging of Cartilage for Osteoarthritis Diagnosis
Authors: Crisford Anna , Cook Hiroki , Bourdakos Konstantinos , Venkateswaran Seshasailam , Dunlop Douglas , Oreffo Richard OC , Mahajan Sumeet
Published: September 2023

Osteoarthritis (OA) is a complex disease of cartilage characterised by chronic joint pain, limitations in mobility and function leading to reduced quality of life. Current methods to diagnose OA, such as X- ray, MRI and the invasive synovial fluid analysis lack molecular specificity and are limited to detection of the late stages of the disease. A rapid minimally invasive and non-destructive approach for early diagnosis of OA is a critical unmet need. Label-free techniques such as Raman Spectroscopy (RS), Coherent anti-Stokes Raman scattering (CARS), Second Harmonic Generation (SHG) and Two Photon Fluorescence (TPF) are increasingly being explored to characterise cartilage tissue. However, current studies are based on whole tissue analysis and do not take into account the different and structurally distinct layers in cartilage. In this work, we used Raman spectroscopy to obtain signatures from superficial and deep layers of healthy and osteoarthritic cartilage obtained from a total of 64 patients (45 OA and 19 controls). Spectra were acquired both in the ‘fingerprint’ region from 700 to 1720 cm-1and high-frequency stretching region from 2500 to 3300 cm-1. Principal component and linear discriminant analysis was used to identify the peaks that contributed the most to classification of the different samples. The most pronounced differences were observed at the proline (855 cm-1and 921 cm-1) and hydroxyproline (877 cm-1and 938 cm-1), sulphated glycosaminoglycan (sGAG) (1064 cm-1and 1380 cm-1) for both control and OA as well as the 1245 cm-1and 1272 cm-1, 1320 cm- 1and 1345 cm-1, 1451 collagen modes in OA samples, consistent with expected collagen structural changes. Classification accuracy based on Raman fingerprint spectral analysis of superficial and deep layer cartilage for controls was found to be 94% and 96%, respectively. OA diseased cartilage was classified with 80% and 87% accuracy based on analysis of the superficial and the deep layers, respectively. Raman spectra from the C-H stretching region (2500-3300 cm-1) did not result in high classification accuracies for OA diseased cartilage. Intriguingly, relatively less differences were found with gender in healthy cartilage indicating that OA brings about significant chemical changes across both genders in both layers. On the other hand, we found significant differences in superficial and deep layer cartilage signatures with age (under 60 and over 60 years). Preliminary images of different layers of cartilage using CARS, SHG and TPF showed Cell clustering in OA, and differences in pericellular matrix and collagen structure in the superficial and the deep layers. The current study demonstrates the potential of Raman Spectroscopy together with multimodal imaging as a potential tool that provides insight into the chemical and structural composition of different layers of cartilage to improve OA diagnosis.
Integrative single-cell analysis of epigenomic and transcriptomic states in patients with systemic sclerosis-associated interstitial lung disease
Authors: Li Shifang , Gong Meijiao
Published: September 2023

Interstitial lung disease is the primary cause of death in individuals who have systemic sclerosis, one of the autoimmune connective tissue diseases. Understanding the pathophysiology of the disease is crucial to developing treatment options. Here, we performed a single-cell multi-omic analysis on lung tissue samples from patients with systemic sclerosis-associated interstitial lung disease (SSC-ILD), profiling chromatin accessibility and gene expression in the same samples and discovering significant cellular heterogeneity. Systemic-venous endothelial cells (ECs) have been shown to be pro-inflammatory and highly active. In addition, it was shown that the transcription factor FOSL2 targets the genes involved in response to unfolded proteins in systemic-venous ECs. Furthermore, we prioritized functional risk variants for systemic sclerosis using a genome-wide association study. Ligand-receptor analysis revealed that ECs significantly increased interaction with B cells via CXCL10-CXCR3 in patients with SSC-ILD. Overall, our analysis emphasizes epigenetic and transcriptional patterns in systemic-venous ECs, which might be beneficial in understanding the pathogenesis of SSC-ILD.
Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study
Authors: Achaiah Andrew , Fraser Emily , Saunders Peter , Hoyles Rachel , Benamore Rachel , Ho Ling-Pei
Published: September 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leukocytes and mortality and FVC decline. Here we question which blood leukocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method.

Methods

Using the CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating) CT algorithm, we determined the correlation between different blood leukocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and TLCO% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression.

Results

Neutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=-0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8-39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre [HR 2.66, 95%CI, 1.35-5.25, p=0.005].

Conclusion

Our study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.

Key messages

WHAT IS ALREADY KNOWN ON THIS TOPIC

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic condition. Recently, several human studies have implicated blood leukocyte levels (monocyte, neutrophil and lymphocyte) with FVC decline and mortality. However, direct association between leukocytes and progression of fibrosis using quantitative CT analysis has not been explored.

WHAT THIS STUDY ADDS

This study explored the association between blood monocytes, neutrophils and lymphocytes against increase in fibrosis over time, measured using a quantitative CT algorithm, CALIPER. We show that levels of blood neutrophil and lymphocytes but not monocytes were associated with greater risk of progression of fibrosis.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE AND/OR POLICY

Our study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.
Social support and ideal cardiovascular health in urban Jamaica: a cross-sectional study
Authors: Blake Alphanso L. , Bennett Nadia R. , McKenzie Joette A. , Tulloch-Reid Marshall K. , Govia Ishtar , McFarlane Shelly R. , Walters Renee , Francis Damian K. , Wilks Rainford J. , Williams David R. , Younger-Coleman Novie O. , Ferguson Trevor S.
Published: September 2023

Recent studies have suggested that high levels of social support can encourage better health behaviours and result in improved cardiovascular health. In this study we evaluated the association between social support and ideal cardiovascular health among urban Jamaicans. We conducted a cross-sectional study among urban residents in Jamaica’s south-east health region. Socio-demographic data and information on cigarette smoking, physical activity, dietary practices, blood pressure, body size, cholesterol, and glucose, were collected by trained personnel. The outcome variable, ideal cardiovascular health, was defined as having optimal levels of ≥5 of these characteristics (ICH-5) according to the American Heart Association definitions. Social support exposure variables included number of friends (network size), number of friends willing to provide loans (instrumental support) and number of friends providing advice (informational support). Principal component analysis was used to create a social support score using these three variables. Survey-weighted logistic regression models were used to evaluate the association between ICH-5 and social support score.

Analyses included 841 participants (279 males, 562 females) with mean age of 47.6 ± 18.42 years. ICH-5 prevalence was 26.6% (95%CI 22.3, 31.0) with no significant sex difference (male 27.5%, female 25.7%). In sex-specific, multivariable logistic regression models, social support score, was inversely associated with ICH-5 among males (OR 0.67 [95%CI 0.51, 0.89], p=0.006) but directly associated among females (OR 1.26 [95%CI 1.04, 1.53], p=0.020) after adjusting for age and community SES. Living in poorer communities was also significantly associated with higher odds of ICH-5 among males, while living communities with high property value was associated with higher odds of ICH among females.

In this study, higher level of social support was associated with better cardiovascular health among women, but poorer cardiovascular health among men in urban Jamaica. Further research should explore these associations and identify appropriate interventions to promote cardiovascular health.
The ABCs of Subarachnoid Hemorrhage Blood Volume Measurement: A Simplified Quantitative Method Predicts Outcomes and Delayed Cerebral Ischemia
Authors: Foettinger Fabian , Sharma Rohan , Salman Saif , Weston Alexander D. , Erickson Bradley J. , Huynh Thien , Tawk Rabih G. , Freeman William D.
Published: September 2023

Background

We sought to develop an easy-to-use quantifiable and more precise method to estimate total blood volume in patients with aneurysmal subarachnoid hemorrhage (SAH) and explore its volumetric extent on incidence of delayed cerebral ischemia (DCI) and poor outcomes by modified Rankin Scale by hospital discharge.

Methods

In this retrospective observational cohort study, we analyzed 277 patients with SAH admitted at our Comprehensive Stroke Center between 2012 and 2022. We derived a mathematical model (Model 1) by measuring SAH basal cisternal blood volume using a ABC/2-derived ellipsoid formula (A=width/thickness, B=length, C=vertical extension) on noncontrast computed tomography (NCCT) in 5 major SAH cisternal compartments. We compared Model 1 (M1) against a manual segmentation method (Model 2) on noncontrast head CT (NCCT). Data were analyzed using logistic regression analysis,ttest, receiver operator characteristic curves (ROC), and area under curve (AUC) analysis.

Results

There was no significant difference in cisternal SAH volume (SAHV) analysis between the two models (p=.14). Average SAHV by M1 was 7.0 mL (95% CI, 5,89-8,09) and lower for good outcome at discharge and 16.6 mL (95% CI, 13.49-19.77) for poor outcome. Volumetric analysis showed that patients with DCI had higher SAHV with 10 mL as a cutoff value (JABC-SAHV-outcome=10.0855 mL and JABC-SAHV-DCI=10.117 mL).

Conclusions

A simplified ABC/2-derived method of SAH blood volume measurement is comparable to manual segmentation, and more importantly, can be performed in low-resource settings. Higher total SAH volumes by ABC/2-derived method were associated with worse outcomes and higher risk of DCI in this study population. A potential dose-response relationship of SAHV blood greater than 10mL appeared to predict worse outcomes and higher risk for DCI. A future larger prospective trial is being planned to validate these results.

Subject codes

[50] Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage; [58] Computerized tomography and Magnetic Resonance Imaging