bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling light collection and pump enhancement from quantum wells with plasmonic metasurfaces using power dependent measurements
Authors: Abdelkhalik Mohamed S , Vaskin Aleksandr , López Toni , Abass Aimi , Gómez Rivas Jaime
Published: March 2023

Low light extraction efficiency (LEE) is the greatest limiting factor for the brightness of reduced-size light-emitting diodes (LEDs) as it limits their emission intensity. In addition, LEDs have a Lambertian emission, which requires secondary optics to control the emission directionality. Plasmonic metasurfaces can introduce a way of manipulating the generated light from LEDs to enhance their LEE and steer the emitted light by reshaping the far-field emission. Here, we fabricate resonant plasmonic metasurfaces on top of a typical blue emitting wafer consisting of InGaN/gallium nitride quantum wells developed for commercial LED devices. The metasurface is separated from the InGaN quantum wells by p-GaN and indium-tin-oxide (ITO) layers with a cumulative thickness of 110 nm. Since this distance value is close to the emission wavelength in the corresponding medium, enhanced near-fields of localized plasmonic resonances do not reach the active region. Despite this, we observe a strong influence of the metasurfaces on the far-field photoluminescence emission from the quantum wells as demonstrated by Fourier imaging. Power-dependent excitation measurements of the samples allow us to retrieve the pump and light collection enhancement factors provided by the plasmonic metasurfaces. We demonstrate that the plasmonic metasurfaces can provide a pump enhancement factor of up to 4.1 and a collection enhancement factor of up to 3.2. We have also performed simulations based on the reciprocity principle and achieved a good qualitative agreement with the experimental results.
Recent developments in 2D materials for energy harvesting applications
Authors: Khandelwal Gaurav , Deswal Swati , Shakthivel Dhayalan , Dahiya Ravinder
Published: March 2023

The ever-increasing demand for energy as a result of the growing interest in applications, such as the Internet of Things and wearable systems, etc, calls for the development of self-sustained energy harvesting solutions. In this regard, 2D materials have sparked enormous interest recently, due to their outstanding properties, such as ultra-thin geometry, high electromechanical coupling, large surface area to volume ratio, tunable band gap, transparency and flexibility. This has given rise to noteworthy advancements in energy harvesters such as triboelectric nanogenerators (TENGs), piezoelectric nanogenerators (PENGs) and photovoltaics based on 2D materials. This review introduces the properties of different 2D materials including graphene, transition metal dichalcogenides, MXenes, black phosphorus, hexagonal boron nitride, metal-organic frameworks and covalent-organic frameworks. A detailed discussion of recent developments in 2D materials-based PENG, TENG and photovoltaic devices is included. The review also considers the performance enhancement mechanism and importance of 2D materials in energy harvesting. Finally, the challenges and future perspectives are laid out to present future research directions for the further development and extension of 2D materials-based energy harvesters.
Minimally invasiveversusopen pancreatic surgery: meta-analysis of randomized clinical trials
Authors: Pfister Matthias , Probst Pascal , Müller Philip C , Antony Pia , Klotz Rosa , Kalkum Eva , Merz Daniela , Renzulli Pietro , Hauswirth Fabian , Muller Markus K
Published: March 2023

Background

Widespread implementation of the minimally invasive technique in pancreatic surgery has proven to be challenging. The aim of this study was to compare the perioperative outcomes of minimally invasive (laparoscopic and robotic) pancreatic surgery with open pancreatic surgery using data obtained from RCTs.

Methods

A literature search was done using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Web of Science; all available RCTs comparing minimally invasive pancreatic surgery and open pancreatic surgery in adults requiring elective distal pancreatectomy or partial pancreatoduodenectomy were included. Outcomes were mortality rate, general and pancreatic surgery specific morbidity rate, and length of hospital stay.

Results

Six RCTs with 984 patients were included; 99.0 per cent (486) of minimally invasive procedures were performed laparoscopically and 1.0 per cent (five) robotically. In minimally invasive pancreatic surgery, length of hospital stay (−1.3 days, −2 to −0.5, P = 0.001) and intraoperative blood loss (−137 ml, −182 to −92, P < 0.001) were reduced. In the subgroup analysis, reduction in length of hospital stay was only present for minimally invasive distal pancreatectomy (−2 days, −2.3 to −1.7, P < 0.001). A minimally invasive approach showed reductions in surgical site infections (OR 0.4, 0.1 to 0.96, P = 0.040) and intraoperative blood loss (−131 ml, −173 to −89, P < 0.001) with a 75 min longer duration of surgery (42 to 108 min, P < 0.001) only in partial pancreatoduodenectomy. No significant differences were found with regards to mortality rate and postoperative complications.

Conclusion

This meta-analysis presents level 1 evidence of reduced length of hospital stay and intraoperative blood loss in minimally invasive pancreatic surgery compared with open pancreatic surgery. Morbidity rate and mortality rate were comparable, but longer duration of surgery in minimally invasive partial pancreatoduodenectomy hints that this technique in partial pancreatoduodenectomy is technically more challenging than in distal pancreatectomy.
Social networks of reintroduced Przewalski’s horses in the Great Gobi B Strictly Protected Area (Mongolia)
Authors: Bernátková Anna , Oyunsaikhan Ganbaatar , Šimek Jaroslav , Komárková Martina , Ceacero Francisco
Published: March 2023

Analyzing social networks is a powerful tool for understanding the ecology of social species. While most studies focus on the role of each group member, few compare groups with different characteristics. The current population of Przewalski’s horses Equus ferus przewalskii at the Great Gobi B Strictly Protected Area (Mongolia) includes groups of wild-born and captive-bred individuals with different experiences with the area (acclimatizing, long-term reintroduced, and wild-born), therefore serving as an ideal natural behavioral lab. We filmed 11 groups for 141.5 hours in summer 2018 (July), late spring 2019 (May, June), and autumn 2019 (September, October). Affiliative and agonistic interactions were recorded, and social networks were created. We tested the influence of origin, experience, season, sex, age, relative time belonging to the group, relatedness, and dominance rank on different network indices at the individual and group levels. We found that groups with greater experience in the area are generally better connected than members of the newly formed groups. However, these strong networks were created by wild-born individuals with very low interaction rates. On the contrary, inexperienced groups composed of captive-bred individuals displayed many interactions but created weak social networks. The results show a trend of behavioral transition from acclimatizing through long-term reintroduced to wild-born groups, supporting that the newly formed groups of released Przewalski’s horses need time to display the typical social behavior patterns of wild-born individuals. Long-term monitoring of released Przewalski’s horses is recommended to promote the success of this reintroduction program.
Left atrial strain analysis improves left ventricular filling pressures non-invasive estimation in the acute phase of Takotsubo syndrome
Authors: Iannaccone Giulia , Graziani Francesca , Del Buono Marco Giuseppe , Camilli Massimiliano , Lillo Rosa , Caffè Andrea , Moroni Francesco , La Vecchia Giulia , Pedicino Daniela , Sanna Tommaso , Trani Carlo , Lombardo Antonella , Lanza Gaetano Antonio , Massetti Massimo , Crea Filippo , Montone Rocco A
Published: March 2023

Aims

The aim of our study is to assess the ability of left atrial (LA) strain values to improve left ventricular and diastolic pressure (LVEDP) non-invasive estimation as compared with traditional echocardiographic indexes in the acute phase of Takotsubo syndrome (TTS) and to predict adverse in-hospital outcomes in this population.

Methods and results

Consecutive TTS patients were prospectively enrolled. Left ventricular and diastolic pressure was measured at the time of catheterization. Transthoracic echocardiography was performed within 48 h from hospital admission. In-hospital complications (acute heart failure, death from any cause, and life-threatening arrhythmias) were collected. A total of 62 patients were analysed (72.2 ± 10.1 years, female 80%) and in-hospital complications occurred in 25 (40.3%). Left ventricular and diastolic pressure mean value was 24.53 ± 7.92 mmHg. Left atrial reservoir and pump strain values presented higher correlation with LVEDP (r −0.859, P < 0.001 and r −0.848, P < 0.001, respectively) in comparison with E/e ′ ratio, left atrial volume index (LAVi), and tricuspid regurgitation (TR) peak velocity. In addition, at receiver-operating characteristic curve analysis, LA reservoir and pump strain resulted to be better predictors of LVEDP above the mean of our population [0.909 (95% CI 0.818–0.999, P < 0.001) and 0.889 (95% CI 0.789–0.988, P < 0.001)], respectively] as compared with E/e′ ratio, LAVi, and TR peak velocity.

Finally, LA reservoir strain resulted to be an independent predictor of worse in-hospital outcomes, together with LVEDP and left ventricular ejection fraction (all P < 0.001).

Conclusion

In our study, lower LA reservoir and pump strain values were better predictors of LVEDP as compared with traditional echocardiographic indexes in the acute phase of TTS syndrome. Moreover, LA reservoir strain was an independent predictor of adverse in-hospital outcomes.
The efficacy of PCSK9 inhibitors on major cardiovascular events and lipid profile in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Imbalzano Egidio , Ilardi Federica , Orlando Luana , Pintaudi Basilio , Savarese Gianluigi , Rosano Giuseppe
Published: March 2023

Objective

To evaluate the specific effects of PCSK9 inhibitors (i.e. alirocumab and evolocumab) on major cardiovascular events (MACE) and lipid profile in patients with diabetes.

Methods and results

We conducted a systematic review of literature according to the PRISMA statement. A total of eight randomized control trials (RCTs) enrolling 20 651 patients with diabetes were included. The mean follow-up was 51 weeks. We included RCTs that had compared the subtilisin–kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab with placebo in subjects with hypercholesterolaemia and diabetes mellitus.

MACE occurred in 8.7% of patients with diabetes randomized to PCSK9i vs. 11.0% of those randomized to placebo. Thus, the use of alirocumab or evolocumab reduced MACE by 18% [odds ratio (OR): 0.82; 95% confidence interval (CI): 0.74–0.90]. Compared with control group, the use of PCSK9 inhibitors was associated with a significant percentage change from baseline in low-density lipoprotein cholesterol [mean difference (MD) –58.48%; 95% CI: –63.73 to –53.22%, P < 0.0001], high-density lipoprotein cholesterol (HDL-C) (MD 5.21%; 95% CI: 3.26–7.17%), triglycerides (MD –14.59%; 95% CI: –19.42 to –9.76%), non-HDL-C (MD –48.84%; 95% CI: –54.54 to –43.14%), and total cholesterol (MD –33.76%; 95% CI: –38.71 to –28.8%). Moreover, a significant reduction of lipoprotein(a) (MD –32.90%; 95% CI: –38.55 to –27.24%) and apolipoprotein B (MD –46.83%; 95% CI: –52.71 to ––40.94%) were observed in PCSK9i group compared with placebo.

Conclusion

PCSK9i appear to be effective in reducing the risk of MACE and in improving lipid profiles of subjects with diabetes and dyslipidaemia.
Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration
Authors: Sprague Briana N , Zhu Xiaonan , Rosso Andrea L , Verghese Joe , Delbaere Kim , Lipnicki Darren M , Sachdev Perminder S , Ng Tze Pin , Gwee Xinyi , Yap Keng Bee , Kim Ki-Woong , Han Ji Won , Oh Dae Jong , Narazaki Kenji , Chen Tao , Chen Sanmei , Brodaty Henry , Numbers Katya , Kochan Nicole A , Walker Richard W , Paddick Stella-Maria , Gureje Oye , Ojagbemi Akin , Bello Toyin , Rosano Caterina ,   for the COSMIC Consortium
Published: March 2023

Background

Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries.

Methods

We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified.

Results

Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women.

Conclusions

This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.
Adjuvant zoledronic acid therapy for postmenopausal women with early breast cancer in China: a cost-effectiveness analysis
Authors: Huang Xiaoting , Liu Yiwei , Lin Shen , Wang Hang , Deng Yujie , Rao Xin , Guo Xianzhong , Jiang Xinchan , Weng Xiuhua , Huang Pinfang
Published: March 2023

Combination therapy of zoledronic acid (ZOL) plus aromatase inhibitor (AI) was found to reduce bone metastasis risk and improve overall survival for treatment-naïve postmenopausal women (PMW) with hormone receptor–positive (HR+) early breast cancer (EBC), when compared with AI alone. The objective of this study was to evaluate the cost-effectiveness of adding ZOL to AI in treating PMW with HR+ EBC in China. A 5-state Markov model was constructed to evaluate the cost-effectiveness of adding ZOL to AI for PMW-EBC (HR+) over a lifetime horizon from the perspective of Chinese healthcare provider. Data used were obtained from previous reports and public data. The primary outcomes of this study were direct medical cost, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed to examine the robustness of the presented model. Over a lifetime horizon, adding ZOL to AI was projected to yield a gain of 1.286 LYs and 1.099 QALYs compared with AI monotherapy, which yielded ICER $11 140.75 per QALY with an incremental cost of $12 247.36. The one-way sensitivity analysis indicated that the cost of ZOL was the most influential factor in our study. The probability that adding ZOL to AI was cost-effective at a threshold of $30 425 per QALY in China was 91.1%. ZOL is likely to be cost-effective in reducing bone metastasis risk and improving overall survival for PMW-EBC (HR+) in China.
Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice
Authors: White Nicole M , Carter Hannah E , Kularatna Sanjeewa , Borg David N , Brain David C , Tariq Amina , Abell Bridget , Blythe Robin , McPhail Steven M
Published: March 2023

Objective

Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations.

Materials and Methods

A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist.

Results

Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups.

Discussion and Conclusion

Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.
Estimating and improving dynamic treatment regimes with a time-varying instrumental variable
Authors: Chen Shuxiao , Zhang Bo
Published: March 2023

Estimating dynamic treatment regimes (DTRs) from retrospective observational data is challenging as some degree of unmeasured confounding is often expected. In this work, we develop a framework of estimating properly defined ‘optimal’ DTRs with a time-varying instrumental variable (IV) when unmeasured covariates confound the treatment and outcome, rendering the potential outcome distributions only partially identified. We derive a novel Bellman equation under partial identification, use it to define a generic class of estimands (termed IV-optimal DTRs) and study the associated estimation problem. We then extend the IV-optimality framework to tackle the policy improvement problem, delivering IV-improved DTRs that are guaranteed to perform no worse and potentially better than a prespecified baseline DTR. Importantly, this IV-improvement framework opens up the possibility of strictly improving upon DTRs that are optimal under the no unmeasured confounding assumption (NUCA). We demonstrate via extensive simulations the superior performance of IV-optimal and IV-improved DTRs over the DTRs that are optimal only under the NUCA. In a real data example, we embed retrospective observational registry data into a natural, two-stage experiment with noncompliance using a differential-distance-based, time-varying IV and estimate useful IV-optimal DTRs that assign mothers to a high-level or low-level neonatal intensive care unit based on their prognostic variables.
UV-DDB stimulates the activity of SMUG1 during base excision repair of 5-hydroxymethyl-2'-deoxyuridine moieties
Authors: Jang Sunbok , Raja Sripriya J , Roginskaya Vera , Schaich Matthew A , Watkins Simon C , Van Houten Bennett
Published: March 2023

UV-damaged DNA-binding protein (UV-DDB) is a heterodimeric protein, consisting of DDB1 and DDB2 subunits, that works to recognize DNA lesions induced by UV damage during global genome nucleotide excision repair (GG-NER). Our laboratory previously discovered a non-canonical role for UV-DDB in the processing of 8-oxoG, by stimulating 8-oxoG glycosylase, OGG1, activity 3-fold, MUTYH activity 4-5-fold, and APE1 (apurinic/apyrimidinic endonuclease 1) activity 8-fold. 5-hydroxymethyl-deoxyuridine (5-hmdU) is an important oxidation product of thymidine which is removed by single-strand selective monofunctional DNA glycosylase (SMUG1). Biochemical experiments with purified proteins indicated that UV-DDB stimulates the excision activity of SMUG1 on several substrates by 4-5-fold. Electrophoretic mobility shift assays indicated that UV-DDB displaced SMUG1 from abasic site products. Single-molecule analysis revealed that UV-DDB decreases the half-life of SMUG1 on DNA by ∼8-fold. Immunofluorescence experiments demonstrated that cellular treatment with 5-hmdU (5 μM for 15 min), which is incorporated into DNA during replication, produces discrete foci of DDB2-mCherry, which co-localize with SMUG1-GFP. Proximity ligation assays supported a transient interaction between SMUG1 and DDB2 in cells. Poly(ADP)-ribose accumulated after 5-hmdU treatment, which was abrogated with SMUG1 and DDB2 knockdown. These data support a novel role for UV-DDB in the processing of the oxidized base, 5-hmdU.
Association Between Candidemia and Noninfectious Interstitial Pneumonia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group
Authors: Kimura Shun-ichi , Akahoshi Yu , Shiratori Souichi , Okinaka Keiji , Harada Kaito , Uchida Naoyuki , Doki Noriko , Ikegame Kazuhiro , Nakamae Hirohisa , Tanaka Masatsugu , Takada Satoru , Kawakita Toshiro , Matsuoka Ken-ichi , Ara Takahide , Ota Shuichi , Sawa Masashi , Onizuka Makoto , Fukuda Takahiro , Atsuta Yoshiko , Kanda Yoshinobu , Nakasone Hideki
Published: March 2023

Background

α-mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in mouse models. This study aimed to evaluate the association between candidemia and noninfectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients.

Methods

Using a Japanese transplant registry database, we analyzed 9143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7531) or second (n = 1612) allogeneic HCT between 2009 and 2019.

Results

Noninfectious IP was observed in 694 patients at a median (range) of 63 (0–1292) days after HCT. Candidemia occurred in 358 patients at a median (range) of 31 (0–903) days after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of noninfectious IP (hazard ratio [HR], 2.51; 95% CI, 1.48–4.25), along with total body irradiation (>8 Gy; HR, 1.57; 95% CI, 1.18–2.10) and malignant lymphoma (vs acute myeloid leukemia; HR, 1.30; 95% CI, 1.004–1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95% CI, 0.45–0.75) and acute lymphoblastic leukemia (vs acute myeloid leukemia; HR, 0.68; 95% CI, 0.49–0.94) were associated with reduced incidence of noninfectious IP. The median survival after the development of noninfectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs 59 days; P < .001).

Conclusions

Candidemia was associated with an increased incidence of noninfectious IP. The prognosis of noninfectious IP after candidemia was extremely poor.
Lamivudine induced pure red cell aplasia and HIV-1 drug resistance-associated mutations: a case report
Authors: Kakubu Mireille A M , Bikinesi Tarisai , Katoto Patrick D M C
Published: March 2023

Adverse effects linked to antiretroviral therapy (ART) may contribute to poor adherence on the patient’s side. Consequently, human immunodeficiency virus (HIV) drug resistance mutations could emerge, negatively impacting the body’s immune system. Meanwhile, severe immunosuppression can lead to several conditions, including anemia. The cause of anemia in HIV infection is multifactorial, and can be mainly explained by deleterious direct effects of the virus on the bone marrow, and opportunistic infections such as Parvovirus B19. Other causes include blood loss resulting from neoplasms and gastrointestinal lesions. Moreover, anemia can also be caused by antiretroviral drugs. We report a case of persistent anemia after ART initiation, kidney injury and treatment failure following a lengthy period of non-adherence to ART. The anemia was classified as Pure Red Cell Aplasia (PRCA). With treatment modification, the anemia resolved and the patient attained virologic suppression. Lamivudine (3TC) was pointed out as the cause of PRCA, which resolved after its withdrawal from the ART regimen. This rare side effect should be investigated in patients on 3TC who present with recurrent anemia.
Ruptured pulmonary hydatid cyst and lophomoniasis comorbidity in a young man: a rare case
Authors: Jalayeri Mohammad H T , Zakariaei Zakaria , Fakhar Mahdi , Sharifpour Ali , Banimostafavi Elham S , Soleymani Mostafa
Published: March 2023

Hydatidosis is a parasitic and zoonotic infection caused by the larval stage of Echinococcus granulosus. Cysts of this parasite involve almost all the organs of the human body, especially the liver and lungs. Asymptomatic cases may develop into symptomatic pulmonary hydatidosis due to the rupture of hydatid cysts. Lophomonas, as causative agents of pulmonary lophomoniasis, is an emerging protozoan that mostly infects the lower respiratory airways. Clinical symptoms of these two diseases can mostly be overlapped. Herein, we describe the rare case of comorbidity of a ruptured cystic echinococcosis and lophomoniasis in a 38-year-old male farmer with a history of opium addiction from northern Iran.
Cognitive heterogeneity reveals molecular signatures of age-related impairment
Authors: Logan Sreemathi , Baier Matthew P , Owen Daniel B , Peasari John , Jones Kenneth L , Ranjit Rojina , Yarbrough Hannah P , Masingale Anthony M , Bhandari Suyesha , Rice Heather C , Kinter Michael T , Sonntag William E
Published: March 2023

The greatest risk factor for cognitive decline is aging. The biological mechanisms for this decline remain enigmatic due, in part, to the confounding of normal aging mechanisms and those that contribute to cognitive impairment. Importantly, many individuals exhibit impaired cognition in age, while some retain functionality despite their age. Here, we establish a behavioral testing paradigm to characterize age-related cognitive heterogeneity in inbred aged C57BL/6 mice and reliably separate animals into cognitively “intact” (resilient) and “impaired” subgroups using a high-resolution home-cage testing paradigm for spatial discrimination. RNA sequencing and subsequent pathway analyses of cognitively stratified mice revealed molecular signatures unique to cognitively impaired animals, including transcriptional down-regulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) and sirtuin (Sirt1 and Sirt3) expression in the hippocampus. Mitochondrial function assessed using high-resolution respirometry indicated a reduced OXPHOS coupling efficiency in cognitively impaired animals with subsequent hippocampal analyses revealing an increase in the oxidative damage marker (3-nitrotyrosine) and an up-regulation of antioxidant enzymes (Sod2, Sod1, Prdx6, etc.). Aged–impaired animals also showed increased levels of IL-6 and TNF-α gene expression in the hippocampus and increased serum levels of proinflammatory cytokines, including IL-6. These results provide critical insight into the diversity of brain aging in inbred animals and reveal the unique mechanisms that separate cognitive resilience from cognitive impairment. Our data indicate the importance of cognitive stratification of aging animals to delineate the mechanisms underlying cognitive impairment and test the efficacy of therapeutic interventions.
Optimal synchronization in pulse-coupled oscillator networks using reinforcement learning
Authors: Chen Ziqin , Anglea Timothy , Zhang Yuanzhao , Wang Yongqiang
Published: March 2023

Spontaneous synchronization is ubiquitous in natural and man-made systems. It underlies emergent behaviors such as neuronal response modulation and is fundamental to the coordination of robot swarms and autonomous vehicle fleets. Due to its simplicity and physical interpretability, pulse-coupled oscillators has emerged as one of the standard models for synchronization. However, existing analytical results for this model assume ideal conditions, including homogeneous oscillator frequencies and negligible coupling delays, as well as strict requirements on the initial phase distribution and the network topology. Using reinforcement learning, we obtain an optimal pulse-interaction mechanism (encoded in phase response function) that optimizes the probability of synchronization even in the presence of nonideal conditions. For small oscillator heterogeneities and propagation delays, we propose a heuristic formula for highly effective phase response functions that can be applied to general networks and unrestricted initial phase distributions. This allows us to bypass the need to relearn the phase response function for every new network.
68Ga-labeled amphiphilic polymer nanoparticles for PET imaging of sentinel lymph node metastasis
Authors: Chen Qin , Fu Xiaomin , Cai Huawei , Fu Shengxiang , Cai Zhongyuan , Li Mufeng , Wu Xiaoai , Tian Rong , Ai Hua
Published: March 2023

Precise diagnosis of lymph node metastasis is important for therapeutic regimen planning, prognosis analysis and probably better outcomes for cancer patients. In this work, 68Ga-labeled amphiphilic alternating copolymers nanoparticles with different rigid ligands were synthesized as positron emission tomography (PET) probes for lymph node metastasis imaging. The labeling efficiency and stability of nanoparticles was improved with increased rigidity of coordination unit. PU(68Ga-L-MDI-PEG) nanoparticles (PU(68Ga-L-MDI-PEG) NPs) with the strongest rigidity of coordination unit exhibited the lowest critical micelle concentration, the best 68Ga labeling efficiency and stability. During in vivo lymph node metastasis imaging, PU(68Ga-L-MDI-PEG) NPs led to different accumulations in normal lymph nodes (N-LN) and tumor metastasized sentinel lymph nodes (T-SLN), which resulted in different PET signal presentation, making it feasible to differentiate N-LN from T-SLN. In comparison, small molecule probe 68GaL had poor lymph node accumulation, not only making it difficult to find lymph nodes on PET/computed tomography scan, but also tough to distinguish N-LN from metastatic ones. Overall, this work provides a reference for design of 68Ga labeled polymeric nanoparticles with high chelation efficiency and stability, as sensitive PET probes for lymph node imaging.
Metabolic disturbances in children with narcolepsy: a retrospective study
Authors: Zhang Min , Thieux Marine , Arvis Laura , Lin Jian-Sheng , Guyon Aurore , Plancoulaine Sabine , Villanueva Carine , Franco Patricia
Published: March 2023

Study objectives

To determine the prevalence of metabolic syndrome (MS) in children with narcolepsy and to evaluate their clinical and sleep characteristics according to the different components of MS.

Methods

This retrospective study consisted of 58 de novo children with narcolepsy (median age: 12.7 years, 48.3% of boys). The recently published MS criteria in a French population of children were used. Clinical and sleep characteristics were compared between groups with different components of MS.

Results

MS was present in 17.2% of children with narcolepsy, among whom 79.3% presented with high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index, 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Patients with at least two MS components had more night eating behaviors and tended to have lower percentage of slow-wave sleep and more fragmented sleep. On multiple sleep latency test, they had shorter mean sleep latencies to rapid eye movement (REM), non-REM sleep and tended to have more sleep onset REM periods (SOREMPs) than those with less than two MS components.

Conclusions

Insulin resistance was found to be the core metabolic disturbance in obese as well as in nonobese children with narcolepsy. Children with narcolepsy with at least two MS components presented a more severe daytime sleepiness and a higher prevalence of night-eating behaviors than those with less than two MS components. Such children might benefit from early evaluation and management in order to prevent future complications.
OpNotes and Clinical Exercises: Activities to Enhance the Clinical Context of the Preclerkship Anatomy Dissection Laboratory
Authors: Meredith M. Alex , Harrell Kelly M. , Foster Kenneth W. , Edwards Cherie , Puche Adam C.
Published: March 2023

Problem

Despite numerous pedagogical approaches and technologies now available for medical gross anatomy, students can find it difficult to translate what occurs in a dissection laboratory into the context of clinical practice.

Approach

Using complementary and collaborative approaches at 2 different medical schools, Virginia Commonwealth University (VCU) and University of Maryland (UM), we designed and implemented a series of clinical activities in the preclerkship medical gross anatomy laboratory that directly link dissected structures to clinical procedures. These activities specifically direct students to perform simulated clinically related procedures on anatomic donors during laboratory dissection sessions. The activities are called OpNotes at VCU and Clinical Exercises at UM. Each activity in the VCU OpNotes requires about 15 minutes of group activity at the end of a scheduled laboratory and involves faculty to grade the student responses submitted via a web-based-assessment form. Each exercise in UM Clinical Exercises also requires about 15 minutes of group activity during the schedule laboratory but does not involve faculty to complete grading.

Outcomes

Cumulatively, the activities in OpNotes and Clinical Exercises both brought clinical context directly to anatomical dissections. These activities began in 2012 at UM and 2020 at VCU, allowing a multiyear and multi-institute development and testing of this innovative approach. Student participation was high, and perception of its effectiveness was almost uniformly positive.

Next Steps

Future iterations of the program will work to assess the efficacy of the program as well as to streamline the scoring and delivery of the formative components. Collectively, we propose that the concept of executing clinic-like procedures on donors in anatomy courses is an effective means of enhancing learning in the anatomy laboratory while concurrently underscoring the relevance of basic anatomy to future clinical practice.
Are all Cages Created Equal? Analysis of Cervical Cage Malfunctions Using FDA MAUDE Database
Authors: Ungurean Victor , Piple Amit S. , Raji Oluwatodimu Richard , Rowland Andrea , Schlauch Adam , Kondrashov Dimitriy G. , Hsu Ken Y. , Zucherman James F.
Published: March 2023

Study Design.

Retrospective case series.

Objective.

To characterize failure rates of cervical cages based on manufacturer and design characteristics using the nationwide database of reported malfunctions.

Background.

The Food and Drug Administration (FDA) aims to ensure the safety and efficacy of cervical interbody implants postimplantation; however, intraoperative malfunctions may be overlooked.

Materials and Methods.

The FDA’s Manufacturer and User Facility Device Experience database was queried for reports of cervical cage device malfunctions from 2012 to 2021. Each report was categorized based on the failure type, implant design, and manufacturer. Two market analyses were performed. First, “failure-to-market share indices” were generated by dividing the number of failures per year for each implant material by its yearly US market share in cervical spine fusion. Second, “failure-to-revenue indices” were calculated by dividing the total number of failures per year for each manufacturer by their approximate yearly revenue from spinal implants in the US. Outlier analysis was performed to generate a threshold value above which failure rates were defined as greater than the normal index.

Results.

In total, 1336 entries were identified, and 1225 met the inclusion criteria. Of these, 354 (28.9%) were cage breakages, 54 (4.4%) were cage migrations, 321 (26.2%) were instrumentation-related failures, 301 (24.6%) were assembly failures, and 195 (15.9%) were screw failures. Poly-ether-ether-ketone implants had higher failure by market share indices for both migration and breakage compared with titanium. Upon manufacturer market analysis, Seaspine, Zimmer-Biomet, K2M, and LDR exceeded the failure threshold.

Conclusion.

The most common cause of implant malfunction was breakage. Poly-ether-ether-ketone cages were more likely to break and migrate compared with titanium ones. Many of these implant failures occurred intraoperatively during instrumentation, which underscores the need for FDA evaluation of these implants and their accompanying instrumentation under the appropriate loading conditions before commercial approval.
The Utility of 18F-NaF-Positron Emission Tomography/Computed Tomography in Measuring the Metabolic Activity of the Aging Spine
Authors: Park Peter Sang Uk , Resto David A. , Khurana Navpreet , Raynor William Y. , Werner Thomas J. , Høilund-Carlsen Poul Flemming , Alavi Abass
Published: March 2023

Study Design.

Cross-sectional; observational.

Objectives.

To determine whether sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) can be used to monitor decreased bone turnover with aging in the spine.

Background.

Osteoporosis is characterized by structural changes in the bone such as decreased bone mineral density leading to an increased risk for fractures. An imaging modality capable of identifying molecular changes that precede these structural changes could be critical for the early diagnosis and monitoring of osteoporosis and other metabolic bone disorders.

Materials and Methods.

The potential of 18F-sodium fluoride (NaF)–PET/CT in detecting changes in bone turnover associated with aging was examined in the lumbar spine of 88 healthy volunteers (43 females, 45 males; mean age 44.6 yr). Regions of interest equal to the trabecular body of the L1 to L4 vertebrae were used to calculate the mean standardized uptake value (SUVmean) and average Hounsfield unit (HU) values. Receiver-operating characteristic curve analysis with an area under the curve using the Wilson/Brown method was generated to assess the value of NaF uptake (SUVmean) in predicting osteoporosis as defined by HU-threshold values. To determine the correlation among global SUVmean, mean HU values, and age, the Spearman correlation test was performed on images acquired at 90 minutes postinjection.

Results.

There was a significant negative correlation between NaF SUVmean and age in females (P < 0.0001, r = −0.59), and a weaker, but also significant correlation in males (P = 0.03, r = −0.32). In females only, there was a significant correlation between NaF uptake and age at all acquisition time points. Measured NaF uptake increased by 10% to 15% with acquisition time in both sexes, from 45 to 90 minutes and from 90 to 180 minutes.

Conclusions.

NaF-PET/CT detects decreased vertebral bone turnover with aging, particularly in females. Measured NaF uptake increased with PET acquisition time after tracer injection, which must be considered in follow-up studies monitoring disease development and treatment effects.
Preoperative Epidural Steroid Injection Does Not Increase Infection Risk Following Posterior Cervical Surgery
Authors: Shelby Tara , Mills Emily S. , Kang Hyunwoo P. , Ton Andy , Hah Raymond J. , Alluri Ram K.
Published: March 2023

Study Design.

Retrospective cohort study.

Objective.

The purpose of this study was to characterize the infection risk of preoperative epidural steroid injection (ESI) in patients undergoing posterior cervical surgery.

Summary of Background Data.

ESI is a helpful tool for alleviating pain and is often used as a diagnostic tool before cervical surgery. However, a recent small-scale study found that ESI before cervical fusion was associated with an increased risk of postoperative infection.

Materials and Methods.

Patients from 2010 to 2020 with cervical myelopathy, spondylosis, and radiculopathy who underwent posterior cervical procedure including laminectomy, laminoforaminotomy, fusion, or laminoplasty were queried from the PearlDiver database. Patients who underwent revision or fusion above C2 or who had a diagnosis of neoplasm, trauma, or preexisting infection were excluded. Patients were divided on whether they received an ESI within 30 days before the procedure and subsequently matched by age, sex, and preoperative comorbidities. The χ2 analysis was used to calculate the risk of postoperative infection within 90 days. Logistic regression controlling for age, sex, Elixhauser Comorbidity Index, and operated levels was conducted within the unmatched population to assess infection risk for injected patients across procedure subgroups.

Results.

Overall, 299,417 patients were identified with 3897 having received a preoperative ESI and 295,520 who did not. Matching resulted in 975 in the injected group and 1929 in the control group. There was no significant difference in postoperative infection rate in those who received an ESI within 30 days preoperatively and those who did not (3.28% vs. 3.78%, odds ratio=0.86, 95% CI: 0.57–1.32, P=0.494). Logistic regression accounting for age, sex, Elixhauser Comorbidity Index, and levels operated demonstrated that injection did not significantly increase infection risk in any of the procedure subgroups.

Conclusions.

The present study found no association between preoperative ESI within 30 days before surgery and postoperative infection in patients undergoing posterior cervical surgery.
Paraspinal Sarcopenia is Associated With Worse Patient-Reported Outcomes Following Laminoplasty for Degenerative Cervical Myelopathy
Authors: Pinter Zachariah W. , Reed Ryder , Townsley Sarah E. , Mikula Anthony L. , Lakomkin Nikita , Kazarian Erick , Michalopoulos Giorgos D. , Freedman Brett A. , Currier Bradford L. , Elder Benjamin D. , Bydon Mohamad , Fogelson Jeremy , Sebastian Arjun S. , Nassr Ahmad N.
Published: March 2023

Study Design.

Retrospective cohort study.

Objective.

The present study is the first to assess the impact of paraspinal sarcopenia on patient-reported outcome measures (PROMs) following cervical laminoplasty.

Background.

While the impact of sarcopenia on PROMs following lumbar spine surgery is well-established, the impact of sarcopenia on PROMs following laminoplasty has not been investigated.

Methods.

We performed a retrospective review of patients undergoing laminoplasty from C4-6 at a single institution between 2010 and 2021. Two independent reviewers utilized axial cuts of T2-weighted magnetic resonance imaging sequences to assess fatty infiltration of the bilateral transversospinales muscle group at the C5-6 level and classify patients according to the Fuchs Modification of the Goutalier grading system. PROMs were then compared between subgroups.

Results.

We identified 114 patients for inclusion in this study, including 35 patients with mild sarcopenia, 49 patients with moderate sarcopenia, and 30 patients with severe sarcopenia. There were no differences in preoperative PROMs between subgroups. Mean postoperative neck disability index scores were lower in the mild and moderate sarcopenia subgroups (6.2 and 9.1, respectively) than in the severe sarcopenia subgroup (12.9, P=0.01). Patients with mild sarcopenia were nearly twice as likely to achieve minimal clinically important difference (88.6 vs. 53.5%; P<0.001) and six times as likely to achieve SCB (82.9 vs. 13.3%; P=0.006) compared with patients with severe sarcopenia. A higher percentage of patients with severe sarcopenia reported postoperative worsening of their neck disability index (13 patients, 43.3%; P=0.002) and Visual Analog Scale Arm scores (10 patients, 33.3%; P=0.03).

Conclusion.

Patients with severe paraspinal sarcopenia demonstrate less improvement in neck disability and pain postoperatively and are more likely to report worsening PROMs following laminoplasty.

Level of Evidence.

3
Below-the-knee Amputation with Targeted Muscle Reinnervation: Operative Technique and Technical Pearls
Authors: Chang Brian L. , Kleiber Grant M.
Published: March 2023

Background:

Postamputation pain from symptomatic neuromas and/or phantom limb pain can have a significant detrimental impact on patients’ quality of life following a major lower extremity amputation. Various methods of physiologic nerve stabilization, such as targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface, have been proposed as the best current techniques to prevent that pathologic neuropathic pain.

Methods:

This article details our institution’s technique that has been performed safely and effectively on over 100 patients. Our approach and rationale for each of the major nerves of the lower extremity are presented.

Results:

In contrast to other described techniques for TMR for below-the-knee amputations, this current protocol does not involve performing transfers on all five major nerves, as one must balance rates of symptomatic neuroma formation and nerve-specific phantom limb pain with needed operative time and surgical morbidity from removing proximal sensory function and denervation of the donor motor nerve branches. This technique also differs significantly from others by performing a transposition of the superficial peroneal nerve to place the neurorrhaphy away from the weight-bearing stump.

Conclusion:

This article details our institution’s approach to physiologic nerve stabilization via TMR at time of below-the-knee amputation.
Artificial PGA/Collagen-based Bilayer Conduit in Short Gap Interposition Setting Provides Comparable Regenerative Potential to Direct Suture
Authors: Li Yu , Takanari Keisuke , Nakamura Ryota , Kambe Miki , Ebisawa Katsumi , Oishi Mayumi , Kamei Yuzuru
Published: March 2023

Background:

The aim of this study was to evaluate whether the Nerbridge, an artificial polyglycolic acid conduit with collagen matrix, is comparable to direct nerve suture in a rat sciatic nerve injury model in a short-gap interposition (SGI) setting.

Methods:

Sixty-six female Lewis rats were randomly divided into the sham group (n = 13); no reconstruction (no-recon) group (n = 13; rat model with 10 mm sciatic nerve defect); direct group (n = 20; rat sciatic nerve injury directly connected by 10-0 Nylon); and SGI group (n = 20; sciatic nerve injury repaired using 5-mm Nerbridge). Motor function and histological recovery were evaluated. The sciatic nerve and gastrocnemius muscle were harvested for quantification of the degree of nerve regeneration and muscle atrophy.

Results:

The SGI and direct groups achieved equal recovery in both functional and histological outcomes. At weeks 3 and 8 postsurgery, there was a significant improvement in the sciatic functional index of the SGI group when compared with that of the no-recon group (P < 0.05). Furthermore, the direct and SGI groups had less muscle atrophy at 4 and 8 weeks postsurgery compared with the no-recon group (P < 0.05). The axon density and diameter at the distal site in the SGI group were significantly higher than that in the no-recon group and comparable to that in the direct and sham groups.

Conclusion:

An artificial nerve conduit has equal potential as direct suture in motor nerve reconstruction when used in the SGI setting.