bluuebunny/crossref_metadata_2025 huggingface dataset:
Indobufen alleviates ischemic stroke injury by regulating transcription factor NRF2 and inhibiting ATG5 expression
Authors: Wang Yang , Bai Ge , Mu Shanshan , Zhang Fenglian , Wang Yan
Published: April 2024

Background

Ischemic stroke (IS) is a detrimental neurological disease and IS lacks valuable methods to recover body function. Indobufen (IND) could alleviate IS. However, the possible mechanism remains undefined.

Methods

SH-SY5Y cells were cultured under the oxygen-glucose deprivation/reoxygenation (OGD/R) environment and then were treated with small interfering RNA (siRNA) of NRF2 and ATG5. The influence of various concentrations of IND (50 μM, 100 μM, 200 μM, and 400 μM) was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined by ELISA. Reactive oxygen species (ROS) production was determined by DCFH-DA staining. The protein levels of LC3II/LC3I, Beclin1, p62, NRF2, and ATG5 were detected by western blot.

Results

IND increased cell viability, while depressed the rate of apoptosis in SH-SY5Y cells of OGD/R environment. IND inhibited autophagy by suppressing the levels of LC3II/LC3I, Beclin1 protein, and increasing p62 protein expression in SH-SY5Y cells of OGD/R environment. IND limited the contents of ROS and MDA, while amplifying the activity of SOD in SH-SY5Y cells with OGD/R exposure. IND also promoted NRF2 expression in OGD/R environment.

Conclusion

IND could inhibit autophagy, oxidative stress, and apoptosis in SH-SY5Y cells with OGD/R exposure, further alleviating IS injury by regulating transcription factor NRF2 and inhibiting ATG5 expression.
The effect of combination treatment with low-intensity shockwave therapy and daily tadalafil on severe erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial
Authors: Kalyvianakis Dimitrios , Mykoniatis Ioannis , Pyrgidis Nikolaos , Kapoteli Paraskeui , Zilotis Filimon , Hatzichristou Dimitrios
Published: April 2024

Background

Patients with severe erectile dysfunction (ED) remain the most challenging group in terms of available noninvasive treatment modalities.

Aim

The study sought to assess the role of combination therapy with low-intensity shockwave therapy (LiST) and daily tadalafil 5 mg in a highly select group of patients with severe vasculogenic ED through a double-blind, randomized trial.

Methods

Forty-eight sexually active men were randomly assigned to 12 sessions of LiST 3 times weekly and tadalafil 5 mg once daily (n = 34) or sham therapy and tadalafil (n = 17) for 4 weeks. Patients were assessed at 1 and 3 months after completion of treatment.

Outcomes

Improvement of erectile function was evaluated through the International Index of Erectile Function–Erectile Function domain (IIEF-EF) or 6-item IIEF and the Sexual Encounter Profile (SEP) diary. The primary outcome was the difference between the groups in the IIEF-EF at 3 months after completion of treatment. Secondary outcomes comprised (1) the difference between the groups in the IIEF-EF at 1 month after completion of treatment, (2) the difference between the groups in the “yes” responses to question 3 of the SEP diary at 1 and 3 months, and (3) the treatment-related adverse events. The number of patients attaining a minimal clinically important difference in the IIEF-EF (improvement of at least 7 points) was also assessed.

Results

After treatment, the absolute scores in the IIEF-EF were higher in patients receiving LiST and tadalafil vs sham therapy and tadalafil both at the 1-month (12.1 ± 2.4 vs 10.2 ± 1.7; P = .002) and at the 3-month (12.9 ± 2.1 vs 10.8 ± 1.8; P < .001) evaluation. Between the 2 groups, the proportion of “yes” responses to question 3 of the SEP diary was not statistically significant, whereas the number of patients attaining a minimal clinically important difference in the IIEF-EF was statistically significant only at the 3-month evaluation. No adverse events occurred.

Clinical Implications

Application of LiST in patients with severe vasculogenic ED receiving daily dose tadalafil may further improve erectile function compared with tadalafil as a stand-alone treatment on the short term.

Strengths and Limitations

Although we provided the first study in the field, severe vasculogenic ED was defined based on medical history and clinical examination and not based on penile ultrasound measures.

Conclusion

The combination of 12 sessions LiST 3 times weekly and daily tadalafil for 4 weeks led to a 2-point difference in the IIEF-EF compared with sham therapy and daily tadalafil among patients with severe vasculogenic ED after 1 and 3 months from completion of treatment.
Receptor for Activated C Kinase 1 counteracts ABSCISIC ACID INSENSITIVE5-mediated inhibition of seed germination and post-germinative growth in Arabidopsis
Authors: Li Zhiyong , Zhang Dayan , Liang Xiaoju , Liang Jiansheng
Published: April 2024

ABSCISIC ACID INSENSITIVE5 (ABI5), a key regulator of the abscisic acid (ABA) signalling pathway, plays a fundamental role in seed germination and post-germinative development. However, the molecular mechanism underlying the repression function of ABI5 remains to be elucidated. In this study, we demonstrate that the conserved eukaryotic WD40 repeat protein Receptor for Activated C Kinase 1 (RACK1) is a novel negative regulator of ABI5 in Arabidopsis. The RACK1 loss-of-function mutant is hypersensitive to ABA, while this phenotype is rescued by a mutation in ABI5. Moreover, overexpression of RACK1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes. RACK1 may also physically interact with ABI5 and facilitate its degradation. Furthermore, we found that RACK1 and the two substrate receptors CUL4-based E3 ligases (DWA1 and DWA2) function together to mediate the turnover of ABI5, thereby efficiently reducing ABA signalling in seed germination and post-germinative growth. In addition, molecular analyses demonstrated that ABI5 may bind to the promoter of RACK1 to repress its expression. Collectively, our findings suggest that RACK1 and ABI5 might form a feedback loop to regulate the homeostasis of ABA signalling in acute seed germination and early plant development.
Impact of a Special Operations Forces Basic Training on Body Composition and Energy Expenditure
Authors: Mullie Patrick
Published: April 2024

Introduction

The Belgian Special Operations Regiment undergoes an 8-week basic training course (SOF Basic Course) following the Military Initiation Phase. The aims of the present study were to estimate energy expenditure and changes in body composition during SOF Basic Course.

Materials and Methods

A multi frequency body composition analyser assessed baseline and endpoint body composition. For the purpose of estimating energy expenditure, 41 participants were fitted with triaxial accelerometers. T-tests were performed on paired and unpaired samples in order to estimate statistical significance. Effect size was estimated with Cohen’s d.

Results

SOF Basic Course was completed by 88 out of 126 participants. The participants’ mean (SD) age was 25.0 (4.1) years, weight was 77.6 (8.6) kg, and body fat percentage was 15.3% (3.3). Body weight of completers decreased from 78.3 (8.8) kg to 76.4 (8.0) kg (P = 0.01). Also, body fat decreased by 3.1 (1.8) kg (P = 0.01), and muscle mass increased by 1.2 (1.7) kg (P = 0.01). There was a decrease in body fat percentage from 15.3% (3.3) to 11.6% (3.4) (P = 0.01), with a Cohen’s effect size of 1.86.

The loss of 3.1 kg of body fat corresponds to a loss of 21,700.0 kcal (90.3 MJ) or 362.0 kcal.d−1 (1.5 MJ.d−1). The mean (SD) energy expenditure by physical activity was 1,943.0 (653.8) kcal.d−1 (14.6 [2.7] MJ.d−1). The average (SD) total energy expenditure was 4,088.0 (710.0) kcal.d−1 (36.8 [3.8] MJ.d−1).

Conclusion

Tactical athletes must perform in hypo-energetic environment. Research in the future should investigate the impact of increased energy intake on body composition.
Discharge Opioid Dose Indirectly Associated With Functional Outcomes 2 Weeks After Shoulder and Knee Arthroscopy in a US Military Sample
Authors: Herrera Germaine F , Patzkowski Jeanne C , Patzkowski Michael S , Giordano Nicholas A , Scott-Richardson Maya , Kent Michael , Highland Krista B
Published: April 2024

Introduction

Postsurgical opioid utilization may be directly and indirectly associated with a range of patient-related and surgery-related factors, above and beyond pain intensity. However, most studies examine postsurgical opioid utilization without accounting for the multitude of co-occurring relationships among predictors. Therefore, this study aimed to identify factors associated with opioid utilization in the first 2 weeks after arthroscopic surgery and examine the relationship between discharge opioid prescription doses and acute postsurgical outcomes

Methods

In this prospective longitudinal observational study, 110 participants undergoing shoulder or knee arthroscopies from August 2016 to August 2018 at Walter Reed National Military Medical Center completed self-report measures before and at 14 days postoperatively. The association between opioid utilization and both patient-level and surgery-related factors was modeled using structural equation model path analysis.

Results

Participants who were prescribed more opioids took more opioids, which was associated with worse physical function and sleep problems at day 14, as indicated by the significant indirect effects of discharge opioid dose on day 14 outcomes. Additional patient-level and surgery-related factors were also significantly related to opioid utilization dose and day 14 outcomes. Most participants had opioid medications leftover at day 14.

Conclusion

Excess opioid prescribing was common, did not result in improved pain alleviation, and was associated with poorer physical function and sleep 14 days after surgery. As such, higher prescribed opioid doses could reduce subacute functioning after surgery, without benefit in reducing pain. Future patient-centered studies to tailor opioid postsurgical prescribing are needed.
Understanding the role of zinc ions on struvite nucleation and growth in the context of infection urinary stones
Authors: Prywer Jolanta , Torzewska Agnieszka , Mielniczek-Brzóska Ewa
Published: April 2024

Taking into account that in recent decades there has been an increase in the incidence of urinary stones, especially in highly developed countries, from a wide range of potentially harmful substances commonly available in such countries, we chose zinc for the research presented in this article, which is classified by some sources as a heavy metal. In this article, we present the results of research on the influence of Zn2+ ion on the nucleation and growth of struvite crystals—the main component of infection urinary stones. The tests were carried out in an artificial urine environment with and without the presence of Proteus mirabilis bacteria. In the latter case, the activity of bacterial urease was simulated chemically, by systematic addition of an aqueous ammonia solution. The obtained results indicate that Zn2+ ions compete with Mg2+ ions, which leads to the gradual replacement of Mg2+ ions in the struvite crystal lattice with Zn2+ ions to some extent. This means co-precipitation of Mg-struvite (MgNH4PO4·6H2O) and Znx-struvite (Mg1-xZnxNH4PO4·6H2O). Speciation analysis of chemical complexes showed that Znx-struvite precipitates at slightly lower pH values than Mg-struvite. This means that Zn2+ ions shift the nucleation point of crystalline solids towards a lower pH. Additionally, the conducted research shows that Zn2+ ions, in the range of tested concentrations, do not have a toxic effect on bacteria; on the contrary, it has a positive effect on cellular metabolism, enabling bacteria to develop better. It means that Zn2+ ions in artificial urine, in vitro, slightly increase the risk of developing infection urinary stones.
Folk psychological attributions of consciousness to large language models
Authors: Colombatto Clara , Fleming Stephen M
Published: April 2024

Technological advances raise new puzzles and challenges for cognitive science and the study of how humans think about and interact with artificial intelligence (AI). For example, the advent of large language models and their human-like linguistic abilities has raised substantial debate regarding whether or not AI could be conscious. Here, we consider the question of whether AI could have subjective experiences such as feelings and sensations (‘phenomenal consciousness’). While experts from many fields have weighed in on this issue in academic and public discourse, it remains unknown whether and how the general population attributes phenomenal consciousness to AI. We surveyed a sample of US residents (n = 300) and found that a majority of participants were willing to attribute some possibility of phenomenal consciousness to large language models. These attributions were robust, as they predicted attributions of mental states typically associated with phenomenality—but also flexible, as they were sensitive to individual differences such as usage frequency. Overall, these results show how folk intuitions about AI consciousness can diverge from expert intuitions—with potential implications for the legal and ethical status of AI.
Evaluating Parliamentary Academic Fellows
Authors: Prabhakar Rajiv
Published: April 2024

Parliamentary Academic Fellowship (PAF) schemes have been introduced to boost knowledge exchange between legislatures and the academy. Evaluations of these schemes are rare. This article evaluates the UK Parliament’s PAF scheme based on interviews with former PAFs, Parliamentary hosts, and the Knowledge Exchange Unit. I find that PAFs and hosts want different things from the scheme. This is part of a wider issue of the differing incentives that academics and Parliamentary staff face in conducting knowledge exchange. Bringing academics and Parliamentary staff closer together means adapting the PAF scheme and exploring other forms of engagement beyond a formal fellowship scheme.
Reference gender-specific neonatal size at birth growth curves for singleton and twin neonates from North India
Authors: Murugesan Ambalakkuthan , Nangia Sushma , Saili Arvind
Published: April 2024

Objectives

To construct reference growth curves for the preterm population from North India and compare it with global charts.

Methods

This prospective study enrolled preterm neonates (23 to 36 weeks) from July 2018 to August 2019 after excluding stillbirths and those with congenital malformations. Anthropometry was performed within 18 hours of birth. Gestation age was assessed by the best estimate of a combination of the last menstrual period, antenatal first-trimester ultrasound, and Expanded New Ballard Score (ENBS). Centile curves were constructed for both genders for twins and singleton neonates separately using the GAMLSS method using R software.

Results

During the study period, of the 14,908 births, 3253 (21.8%) were born preterm. After excluding malformations and stillbirths, 2976 preterm neonates were eligible, out of which anthropometry within 18 hours was done for 2719 neonates. Data was analyzed for 2290 singleton and 414 twin preterm neonates. Smoothed reference growth curves were constructed for all anthropometric parameters for both genders for singleton as well as twin neonates. Indian preterm infants were smaller compared to international standards. The proportion of small for gestational age (SGA) neonates was 23.1% (Fenton’s charts) but only 10.9% when the data from the newly constructed chart was used. The concordance with international standards was better for very preterm neonates <32 weeks than moderate and late preterm neonates (32 to 36 weeks).

Conclusions

The reference charts derived from the present study can be used for the North Indian preterm population. The use of western growth charts tends to overestimate the incidence of SGA.
Improving the sampling of red Noctiluca scintillans to understand its impact on coastal ecosystem dynamics
Authors: Kordubel Katharina , Baschek Burkard , Hieronymi Martin , Voynova Yoana G , Möller Klas O
Published: April 2024

Recently, natural and anthropogenic pressures caused an apparent increase in the frequency and spread of red Noctiluca scintillans (RNS) blooms. Here, we describe this potential expansion and the associated environmental factors based on an extensive literature review (1857–2023). Our analysis suggests that Noctiluca increased over time in several Australian, Chinese and European coastal regions. We point to eutrophication, ocean warming and deoxygenation as possible drivers of these intensifications. Moreover, we demonstrate Noctiluca’s importance for coastal ecosystems: with competitive advantages causing fast and intense blooms, Noctiluca has the potential to alter plankton communities, influencing productivity in affected areas. Throughout our analysis, we identified major knowledge gaps that are relevant to assess Noctiluca: (i) challenges in determining its spatiotemporal evolution; (ii) limited knowledge about drivers triggering and ending blooms; (iii) scarce information about feeding, reproduction and interaction in situ and (iv) uncertainty regarding its contribution to carbon export. We hypothesize that these gaps are related to limitations in traditional sampling techniques, and we highlight the need for a holistic approach combining traditional with novel techniques like remote sensing and underwater cameras. Our suggested approach could help filling the identified gaps and facilitate predictions of bloom dynamics and impacts under future climate conditions.
Needle infiltration assisted explantation technique for peripheral nerve stimulator leads
Authors: Nia Sam , Adler Alexandra , Scemama Pascal , Yalamuru Bhavana
Published: April 2024

Introduction

Peripheral nerve stimulation is a neuromodulation modality that is increasing used to treat chronic pain. The permanent peripheral nerve stimulator systems, while easy to implant, are designed to stay in place and scar at the implantation site. There is a paucity of literature on explantation techniques for peripheral nerve stimulators.

Methods

In this report, we describe a needle infiltration assisted technique for lead explantation. This novel technique is minimally invasive, cost-effective, and utilizes a combination of fluoroscopy and ultrasound imaging. We describe the successful use of this technique in 3 cases without any adverse events.

Conclusion

There are many situations which might require a permanent peripheral nerve stimulator to be explanted such as infection, lead erosion, patient request, or need for the patient to undergo magnetic resonance imaging. In these scenarios, we propose a novel needle infiltration assisted technique of explantation that is safe, effective, and easy to replicate.
Analytical insights into semi-infinite plate scattering: the wiener–hopf technique and two-sided linear boundary conditions
Authors: Hales A D G , Ayton L J
Published: April 2024

The Wiener–Hopf Technique is popular throughout applied mathematics, particularly for wave scattering problems. One such problem is the scattering of an incident wave impinging upon a semi-infinite surface. For scattering problems in which one applies separate boundary conditions on each side of the diffraction medium, we must adapt the standard Wiener–Hopf approach via a generalised technique to deal with the resulting matrix system. Such problems are present in the literature, where the Wiener–Hopf problem is reduced to solving Hilbert equations, leading to the so-called Wiener–Hopf–Hilbert method. However, both boundaries tend to have the same mathematical form, which is overly simplistic when describing realistic compliant boundaries or surface coatings. In some other literature, the matrix factorization problem remains the focus and is solved for arbitrary entries, which may prove challenging to use in complex scattering problems. We solve a more general problem while keeping an applied scattering framework, drawing attention to the additional analytical considerations needed to adapt previous methods. More specifically, we study the Wiener–Hopf matrix kernel, which shows that it holds the key to distinguishing these problems from those studied in previous literature. Finally, we present an example of a sound wave scattering off a plate that has a one-sided surface coating and is in flow. We treat this as a two-sided boundary and model the upper side with the Ingard–Myers impedance boundary condition and the lower side with the rigid Neumann boundary condition. Results are presented using impedance values from existing literature that reflect real materials.
A simple construction of potential operators for compensated compactness
Authors: Raiță Bogdan
Published: April 2024

We give a short proof of the fact that each homogeneous linear differential operator $\mathscr{A}$ of constant rank admits a homogeneous potential operator $\mathscr{B}$, meaning that $$\ker\mathscr{A}(\xi)=\mathrm{im\,}\mathscr{B}(\xi) \quad\text{for }\xi\in\mathbb{R}^n\backslash\{0\}.$$ We make some refinements of the original result and some related remarks.
Interpreting Statutes in a Manner Consistent with Seychelles’ International Obligations: Analysing the Court of Appeal’s Decision in The Anti-Corruption Commission of Seychelles v Laura Valabhji (2023)
Authors: Mujuzi Jamil Ddamulira
Published: April 2024

The Constitution of Seychelles requires courts, when interpreting the Charter of Human Rights, to take judicial notice of human rights treaties. However, a similar obligation is not imposed on courts when interpreting legislation. Before the case of The Anti-Corruption Commission of Seychelles v Laura Valabhji (18 December 2023), the Court of Appeal had never held that courts are obliged to interpret statutes to conform to Seychelles’ international obligations. The Court rejected a literal approach to statutory interpretation and favoured a purposive approach to justify its reliance on an international treaty when interpreting the Anti-Corruption Act. In this article, the author argues that the Court’s decision in Anti-Corruption Commission of Seychelles v Laura Valabhji has three challenges: it did not explain the meaning of international obligations; its reliance on Indian and Sri-Lankan cases as a source of common law for Seychelles ignores, not only the Interpretation and General Provisions Act, but also the distinction between foreign cases as a source of common law and foreign cases from common law countries as persuasive authorities; and finally, its failure to define ‘control’ has the effect of expanding the powers of the Anti-Corruption Commission beyond what was envisaged by the legislature.
Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels or blood coagulation
Authors: Muchiri Ruth N , Rocha Jackie , Tandon Ankit , Chen Yongmei Luo , Alemani Rebecca , Ahmad Intakhar , McDonald Zachary , Lindeblad Matthew , Rubinstein Israel , van Breemen Richard B , Feinstein Douglas L
Published: April 2024

Administration of high-dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anticoagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, or increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anticoagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.
Seasonal patterns of nonstructural carbohydrate storage and mobilization in two tree species with distinct life-history traits
Authors: Lu Long-Long , Liu Hao , Wang Jing , Zhao Kun-Peng , Miao Yuan , Li Hai-Chang , Hao Guang-You , Han Shi-Jie
Published: April 2024

Nonstructural carbohydrates (NSC) are essential for tree growth and adaptation, yet our understanding of the seasonal storage and mobilization dynamics of whole-tree NSC is still limited, especially when tree functional types are involved. Here, Quercus acutissima Carruth. and Pinus massoniana Lamb, with distinct life-history traits (i.e. a deciduous broadleaf species vs an evergreen coniferous species), were studied to assess the size and seasonal fluctuations of organ and whole-tree NSC pools with a focus on comparing differences in carbon resource mobilization patterns between the two species. We sampled the organs (leaf, branch, stem and root) of the target trees repeatedly over four seasons of the year. Then, NSC concentrations in each organ were paired with biomass estimates from the allometric model to generate whole-tree NSC pools. The seasonal dynamics of the whole-tree NSC of Q. acutissima and P. massoniana reached the peak in autumn and summer, respectively. The starch pools of the two species were supplemented in the growing season while the soluble sugar pools were the largest in the dormant season. Seasonal dynamics of organ-level NSC concentrations and pools were affected by organ type and tree species, with above-ground organs generally increasing during the growing season and P. massoniana roots decreasing during the growing season. In addition, the whole-tree NSC pools of P. massoniana were larger but Q. acutissima showed larger seasonal fluctuations, indicating that larger storage was not associated with more pronounced seasonal fluctuations. We also found that the branch and root were the most dynamic organs of Q. acutissima and P. massoniana, respectively, and were the major suppliers of NSC to support tree growth activities. These results provide fundamental insights into the dynamics and mobilization patterns of NSC at the whole-tree level, and have important implications for investigating environmental adaptions of different tree functional types.
Hiding in Plain Sight: A Widespread Native Perennial Harbors Diverse Haplotypes of ‘Candidatus Liberibacter solanacearum’ and Its Potato Psyllid Vector
Authors: Kenney Jaimie R. , Shates Tessa , Gebiola Marco , Mauck Kerry E.
Published: April 2024

The unculturable bacterium ‘ Candidatus Liberibacter solanacearum’ (CLso) is responsible for a growing number of emerging crop diseases. However, we know little about the diversity and ecology of CLso and its psyllid vectors outside of agricultural systems, which limits our ability to manage crop disease and understand the impacts this pathogen may have on wild plants in natural ecosystems. In North America, CLso is transmitted to crops by the native potato psyllid ( Bactericera cockerelli). However, the geographic and host plant range of the potato psyllid and CLso beyond the borders of agriculture are not well understood. A recent study of historic herbarium specimens revealed that a unique haplotype of CLso was present infecting populations of the native perennial Solanum umbelliferum in California decades before CLso was first detected in crops. We hypothesized that this haplotype and other potentially novel CLso variants are still present in S. umbelliferum populations. To test this, we surveyed populations of S. umbelliferum in Southern California for CLso and potato psyllid vectors. We found multiple haplotypes of CLso and the potato psyllid associated with these populations, with none of these genetic variants having been previously reported in California crops. These results suggest that CLso and its psyllid vectors are much more widespread and diverse in North American natural plant communities than suggested by data collected solely from crops and weeds in agricultural fields. Further characterization of these apparently asymptomatic haplotypes will facilitate comparison with disease-causing variants and provide insights into the continued emergence and spread of CLso.
Dual Joystick Technique for Reduction of Torsional Profile in Pediatric Supracondylar Humerus Fracture With Delayed Presentation
Authors: Kaganur Raghavendra , Jaisankar Pragadeeshwaran , Sarkar Bhaskar , Paul Nirvin , Azam Md Quamar
Published: April 2024

Background:

Reduction of some modified Gartland type III and IV supracondylar humerus fractures can pose difficulties, especially if they present late to the hospital. Various techniques of reduction have been tried for reducing the supracondylar humerus fracture for sagittal and coronal plane correction. This retrospective study assesses the dual joystick technique’s possible effectiveness in achieving an anatomical reduction of the supracondylar humerus fracture.

Methods:

Patients with modified Gartland’s type III and IV supracondylar humerus fractures who underwent closed reduction and percutaneous pinning using the dual joystick technique at our trauma center between January 2020 and January 2022 were the subject of a retrospective review. Forty-six patients treated by the above technique who met the inclusion criteria were analyzed at the end of the final follow-up.

Results:

The mean age of the children was 7.9+/− 2.25 years, with a male predominance at 32:14. The Right upper limb was more involved compared to the left side. The mean injury to hospital presentation was 2.67+/− 1.28 days, and the mean surgical duration was 24.57+/− 13.76 minutes. The average pin spread ratio at the fracture site was 35.17+/− 3.04%. Baumann angle at the final follow-up was 74.83+/− 2.56 degrees. The mean lateral rotation percentage was 2.8+/− 1.3%. 39 patients had excellent cosmetic outcomes, and 42 had excellent functional outcomes, whereas 7 and 4 patients had good cosmetic and functional outcomes, respectively, according to Flynn criteria.

Conclusions:

In modified Gartland type III and IV fractures with late presentation where reduction is challenging, this technique is shown to be convenient and easily reproducible and helps accomplish near anatomical reduction with reduced lateral rotation percentage and results in excellent to good outcomes.
Nebivolol, an antihypertensive agent, has new application in inhibiting melanoma
Authors: Yang Shuping , Li Zhi , Yi Jiamei , Pan Mingyue , Cao Weiling , Ma Jing , Zhang Peng
Published: April 2024

Repurposing existing drugs for cancer therapy has become an important strategy because of its advantages, such as cost reduction, effect and safety. The present study was designed to investigate the antimelanoma effect and possible mechanisms of action of nebivolol, which is an approved and widely prescribed antihypertensive agent. In this study, we explored the effect of nebivolol on cell proliferation and cell activity in melanoma in vitro and the potential antimelanoma mechanism of nebivolol through a series of experiments, including the analysis of the effects with regard to cell apoptosis and metastasis. Furthermore, we evaluated the antimelanoma effect on xenograft tumor models and inspected the antimelanoma mechanism of nebivolol in vivo using immunohistochemical and immunofluorescence staining assays. As results in this work, in vitro, nebivolol possessed a strong activity for suppression proliferation and cell cycle arrest on melanoma. Moreover, nebivolol significantly induced cell apoptosis in melanoma through a mitochondrial-mediated endogenous apoptosis pathway. Additionally, nebivolol inhibited melanoma cell metastasis. More importantly, nebivolol exhibited significantly effective melanoma xenograft models in vivo, which related to the mechanism of apoptosis induction, proliferation inhibition, metastasis blocking and angiogenesis arrest. Overall, the data of the present study recommend that nebivolol holds great potential in application as a novel agent for the treatment of melanoma.
GPRC5A promotes paclitaxel resistance and glucose content in NSCLC
Authors: Wang Yan , Gao Liang , Wang Feiyu , Yu Cunjun , Chen Chen , Xia Chunwei
Published: April 2024

Lung cancer is one of the most common and malignant cancers worldwide. Chemotherapy has been widely used in the clinical setting, and paclitaxel is the first-line therapy for lung cancer patients but paclitaxel resistance is the main problem. First, we successfully established paclitaxel-resistant lung cancer cells treated with elevated doses of paclitaxel for 3 months, as confirmed by the CCK-8 assay. Paclitaxel-resistant cancer cells increased glucose content. Second, Gtex, Oncomine, and gene expression omnibus database data mining identified GPRC5A, G protein-coupled receptor, as the most prominent differentially expressed gene in drug-resistant datasets including gemcitabine, paclitaxel, and gefitinib overlapped with the microarray data from cancer cell metabolism. Third, qPCR analysis and western blot technique showed that GPRC5A mRNA and protein levels were significantly enhanced in paclitaxel-resistant lung cancer cells. Fourth, functional analysis was conducted by siRNA-mediated transient knockdown of GPRC5A. Silencing GPRC5A significantly decreased paclitaxel resistance and glucose content. In the end, retinoic acid substantially upregulated GPRC5A proteins and promoted glucose content in two lung cancer cells. Kaplan–Meier plot also confirmed that lung cancer patients with high expression of GPRC5A had a relatively lower survival rate. Our study provided a potential drug target GPRC5A, which may benefit lung cancer patients with acquired paclitaxel resistance in the future and a theoretical basis for future preclinical trials.
Intracranial hemorrhage caused by dabrafenib and trametinib therapy for metastatic melanoma
Authors: Hennemann Aymeric , Puzenat Eve , Decreuse Marion , Vuillier Fabrice , Nardin Charlée , Aubin François
Published: April 2024

Although generally well tolerated compared with chemotherapy, molecular targeted therapy used in metastatic melanoma may be associated with life-threatening toxicity. We report the case of a patient with metastatic melanoma treated by dabrafenib plus trametinib who developed intracranial hemorrhage. Physicians should be aware of this rare but life-threatening adverse event of B-rapidly accelerated fibrosarcoma (BRAF) and mitogen-activated protein kinase kinase (MEK). However, they should be careful about the bleeding origin, which can prove to be a new onset of melanoma metastasis or anticoagulation overdose, or even an uncontrolled arterial hypertension.
Challenging Case: New-Onset Hallucinations and Developmental Regression in a Child with Autism Spectrum Disorder
Authors: Sharma Aanchal , Pappas Demetra , Gonzalez-Heydrich Joseph , Sullivan Nancy R. , Nyp Sarah S.
Published: April 2024

CASE:

Nick is a 5-year-old boy who began displaying self-stimulating behaviors and decreased social interactions shortly before turning 3 years. At the age of 3.5 years, he was diagnosed with autism spectrum disorder by a local developmental-behavioral pediatrician. His parents recall that the physician described Nick to be “high functioning” and encouraged them to expect that he would attend college and live independently as an adult. Upon receiving the diagnosis, intervention was initiated using an applied behavioral analysis (ABA) approach. With this intervention, he demonstrated initial gains in the use of complex language and improved social interactions.

Concerns regarding suspected psychosis emerged just before starting kindergarten when Nick began experiencing ego-dystonic visual and auditory hallucinations. Initially, Nick verbally responded to the hallucinations and vividly described what he was experiencing. Shortly after the onset of these hallucinations, Nick experienced a significant decrease in the frequency and complexity of his expressive language and became more withdrawn. Over time, his hallucinations intensified, and his parents became increasingly fearful for his safety. Various antipsychotic and mood-stabilizing medications, steroids, and immunotherapy have been trialed with limited improvement of his symptoms.

An extensive medical evaluation yielded the following:

1. Magnetic resonance imaging of the brain: dilated perivascular spaces.

2. Urine organic acids: ketosis and increased lactic acid.

3. Antinuclear antibody: minimally positive.

4. Vitamin B12: elevated.

All other studies, including lumbar puncture, electroencephalogram (awake and asleep), genetic studies (chromosomal microarray, fragile X testing, and whole exome sequencing), metabolic studies, inflammatory markers, and thyroid panel, were negative/normal.

Nick is enrolled in a special education classroom within a school that utilizes an ABA-based approach for all students. As part of his educational programming, he receives 25 hours of ABA in a 1:1 setting, 2 hours of speech therapy, 3 hours of occupational therapy, 1 hour of physical therapy, and 30 minutes of music therapy weekly. Current concerns include significant head-banging and thrashing before falling asleep, hyperactivity, unsafe behaviors (e.g., banging on windows, climbing high to reach desired items), aggression toward caregivers, limited ability to complete self-care tasks (e.g., personal hygiene, toileting), significant decline in expressive language, and continued response to internal stimuli.

Nick's parents now present to a multidisciplinary center seeking guidance regarding additional therapies/interventions to assist in management of his current developmental and behavioral challenges as well as information regarding his expected developmental trajectory as he reaches adulthood.
Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma
Authors: Ryan Michael P. , Winsett Frank T. , Armenta Andrew M. , Goodwin Brandon P. , Wagner Richard F.
Published: April 2024

BACKGROUND

Although there is a large body of literature regarding risk stratification and outcomes for perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC), there is a relative paucity of studies exploring the role of lymphovascular invasion (LVI) in cSCC and a lack of clear evidence-based guidelines for how to manage patients with these tumors.

OBJECTIVE

This article is intended to review the available literature regarding LVI in cSCC and formulate evidence-based recommendations for clinical management.

METHODS AND MATERIALS

A literature review was conducted using PubMed to find relevant articles relating to outcomes and management of primary cSCC with LVI.

RESULTS

The available literature suggests that LVI is a major risk factor for poor outcomes and increased morbidity and mortality in cSCC.

CONCLUSION

Lymphovascular invasion is a very high-risk feature that should place these tumors in the highest-risk category, and management of these tumors should be similar to that of squamous cell carcinoma with PNI.
The application of artificial intelligence in EUS
Authors: Zhang Deyu , Wu Chang , Yang Zhenghui , Yin Hua , Liu Yue , Li Wanshun , Huang Haojie , Jin Zhendong
Published: April 2024

Artificial intelligence (AI) is an epoch-making technology, among which the 2 most advanced parts are machine learning and deep learning algorithms that have been further developed by machine learning, and it has been partially applied to assist EUS diagnosis. AI-assisted EUS diagnosis has been reported to have great value in the diagnosis of pancreatic tumors and chronic pancreatitis, gastrointestinal stromal tumors, esophageal early cancer, biliary tract, and liver lesions. The application of AI in EUS diagnosis still has some urgent problems to be solved. First, the development of sensitive AI diagnostic tools requires a large amount of high-quality training data. Second, there is overfitting and bias in the current AI algorithms, leading to poor diagnostic reliability. Third, the value of AI still needs to be determined in prospective studies. Fourth, the ethical risks of AI need to be considered and avoided.
Treatment and follow-up of melanoma in situ in a geriatric patient that is a nonsurgical candidate
Authors: Zimmerman Brittany
Published: April 2024

Background: The standard of care for melanoma in situ is a wide excision with at least 0.5 cm margins. These melanomas can be large in size, and some elderly patients are not good surgical candidates so alternative treatment options have been explored. Topical imiquimod is currently approved by the Federal Drug Administration for the treatment of actinic keratosis, external anogenital warts, and superficial basal cell carcinoma. In some patients, treatment with topical imiquimod for malignant melanoma in situ has been shown to be successful. Case report: A 97-year-old male patient presented to a dermatology office with a 4.5×4.0 cm malignant melanoma in situ. The patient was given treatment options of excision and radiation therapy but refused due to his advanced age and desire to avoid extensive surgery. The patient agreed to topical treatment with imiquimod cream 5 times weekly for 5 months. A post-treatment repeat biopsy showed no evidence of residual malignant melanoma in situ. Continued post-treatment follow-up at 3-month internals with pigmented lesion assay(s) and repeat biopsies showed no evidence of recurrence at 1 year. Conclusions: In geriatric patients with a large-sized melanoma in situ that are not good surgical candidates, treatment with topical imiquimod should be considered. Long-term follow-up with pigmented lesion assay(s) should be considered in these patients to help avoid biopsy fatigue, wound management, and complications from comorbidities.
Real-world insights for the evolving intervention strategy for non-mild acute pancreatitis: 35-year experience in a Chinese Tertiary Center
Authors: Yan Xiaxiao , Zhou Jingya , Cao Jian , Xu Qiang , Han Xianlin , Wang Duan , Zhang Shengyu , Wu Dong
Published: April 2024

Background:

With the accumulation of experience and evidence, guidelines for invasive intervention for acute pancreatitis (AP) have continuously evolved, followed in Peking Union Medical College Hospital (PUMCH). We aimed to review AP case series to help understand the impact of guideline evolution on the management and prognosis of AP in real-world practice.

Methods:

This was a single-center study of AP patients who had received invasive interventions from 1988 to 2022. Patient demographics, baseline severity, imaging findings, and the indication, timing, and specific modalities of invasive interventions were collected. The composite primary endpoint was death during hospitalization or major complications after intervention. Other endpoints included pancreatic fistula, incision infection, number of interventions, length of intensive care stay, length of hospitalization, and total medical cost.

Results:

A total of 195 patients were included. The most common indication for invasive intervention was suspected infection, followed by persistent symptoms. The step-up and delayed strategies reduced the incidence of major complications or death. Over 35 years, the number of patients requiring surgery has gradually declined, and more patients need only minimally invasive procedures for remission. The incidence of the primary outcome decreased as well as the duration of hospitalization.

Conclusions:

The management of AP patients at PUMCH in the last 35 years has undergone therapeutic guideline changes that support the efficacy and safety of the deferred step-up strategy in real-world practice.
Understanding acute pancreatitis in end-stage renal disease: unraveling etiologies, clinical presentations, management strategies, and complications—a narrative review
Authors: Lahoud Chloe , Morcos Zeina , Njeim Ryan , Tawfik Mark , Aslam Taimur , El-Sayegh Suzanne
Published: April 2024

Acute pancreatitis (AP) is a common disease with defined diagnostic criteria, radiological findings, and management guidelines. Patients with end-stage renal disease (ESRD) are at an increased risk of developing AP. The diagnosis of AP in ESRD is challenging, and the clinical presentation may mimic other pathologies. Moreover, the impact of AP on the overall morbidity and mortality in ESRD patients warrants a tailored therapeutic approach. We conducted a literature search for published manuscripts on AP and ESRD up to November 2023 in several databases such as Google Scholar and PubMed, and employed the following search terms: “acute pancreatitis,” “pancreatitis,” “end-stage renal disease,” “hemodialysis,” “peritoneal dialysis,” “diagnostic criteria,” “etiology,” “presentation,” “management,” “complication,” “prognosis,” “mortality.” Qualitative and quantitative data were both extracted. This article reviews current evidence-based literature about the etiology and clinical presentation of AP in ESRD. It sheds the light on the current clinical studies that reflect beneficial management strategies as well as complications of AP in ESRD. Patients with ESRD are more likely to develop AP and subsequently severe pancreatitis with high mortality rates compared to the general population. The etiology of AP in ESRD is multifactorial and management is focused on pain control, early nutritional support and most importantly maintaining a fluid balance. While existing research has shed light on certain aspects of AP in ESRD, additional literature focused on this topic is required to foster a deeper and broader understanding of AP in ESRD.
Management of Left Ventricular Intramural Hematoma- an Unusual Complication of Complete Atrioventricular Septal Defect Repair in a Child
Authors: Karanam Sandeep , Wang Justin , Rocha Barnabe , Semple Thomas , Krupickova Sylvia , Desai Ajay
Published: April 2024

Postoperative survival for complete atrioventricular septal defect (cAVSD) is excellent. Common complications of surgery include valvular stenosis/regurgitation, left ventricular outflow tract obstruction, arrythmias, and residual defects. We report a challenging case of a 7-month old girl with Trisomy 21, preoperative obstructive sleep apnea with severe pulmonary hypertension, who underwent AVSD repair and required veno-arterial extracorporeal membrane oxygenation (V-A ECMO) while unable to come off cardiopulmonary bypass and developed left ventricular intramural hematoma during the course. This case highlights the challenges in management of an unusual complication.
A molecular journey on the pathogenesis of primary hyperoxaluria
Authors: Cellini Barbara
Published: April 2024

Purpose of review

Primary hyperoxalurias (PHs) are rare disorders caused by the deficit of liver enzymes involved in glyoxylate metabolism. Their main hallmark is the increased excretion of oxalate leading to the deposition of calcium oxalate stones in the urinary tract. This review describes the molecular aspects of PHs and their relevance for the clinical management of patients.

Recent findings

Recently, the study of PHs pathogenesis has received great attention. The development of novel in vitro and in vivo models has allowed to elucidate how inherited mutations lead to enzyme deficit, as well as to confirm the pathogenicity of newly-identified mutations. In addition, a better knowledge of the metabolic consequences in disorders of liver glyoxylate detoxification has been crucial to identify the key players in liver oxalate production, thus leading to the identification and validation of new drug targets.

The research on PHs at basic, translational and clinical level has improved our knowledge on the critical factors that modulate disease severity and the response to the available treatments, leading to the development of new drugs, either in preclinical stage or, very recently, approved for patient treatment.