A primal-dual splitting algorithm for composite monotone inclusions with minimal lifting.

In this work, we study resolvent splitting algorithms for solving composite monotone inclusion problems. The objective of these general problems is finding a zero in the sum of maximally monotone operators composed with linear operators. Our main contribution is establishing the first primal-dual splitting algorithm for composite monotone inclusions with minimal lifting. Specifically, the proposed scheme reduces the dimension of the product space where the underlying fixed point operator is defined, in comparison to other algorithms, without requiring additional evaluations of the resolvent operators. We prove the convergence of this new algorithm and analyze its performance in a problem arising in image deblurring and denoising. This work also contributes to the theory of resolvent splitting algorithms by extending the minimal lifting theorem recently proved by Malitsky and Tam to schemes with resolvent parameters.

Successive Waves of the COVID-19 Pandemic Had an Increasing Impact on Chronic Cardiovascular Patients in a Western Region of Romania.

Three years since the COVID-19 pandemic started, there is still little information about patients with chronic medical conditions, such as cardiovascular diseases (CVDs), who become infected with SARS-CoV-2. A retrospective analysis was performed to evaluate the impact of the COVID-19 pandemic on patients with cardiovascular comorbidities hospitalized with positive RT-PCR results for SARS-CoV-2 during the highest peaks of the first three pandemic waves: April 2020, October 2020, and November 2021. The primary outcome was in-hospital mortality; the secondary outcomes were length of hospitalization and required mechanical ventilation to assess the disease severity. Data were extracted from the hospital electronic database system: 680 eligible cases were identified out of 2919 patients. Mortality was the highest in wave 3 (31.9%) compared to the previous waves (13.6% and 25.8%). Hospitalization was also significantly longer in wave 3 (11.58 ± 5.34 vs. 8.94 ± 4.74 and 10.19 ± 5.06; p < 0.001), and so was the need for mechanical ventilation (21.7% vs. 8.2% and 9%; p < 0.001). Older age and male gender were confirmed as highly significant predictors of unfavorable outcomes. Ischemic heart disease worsened the odds of patients' survival irrespective of the three pandemic waves (Breslow-Day test, p = 0.387), with a marginally significant Mantel-Haenszel common estimate for risk: OR = 1.604, 95% (0.996; 2.586). The significantly worse outcomes in wave 3 could have been influenced by a combination of factors: the low percentage of vaccinations in Romanian population, the more virulent delta strain, and pandemic attrition in the care provided to these patients with chronic CVDs.

The chronic coronary syndrome-Heart failure roundabout: A multimodality imaging workflow approach.

Heart failure (HF) is a complex syndrome of considerable burden with high mortality and hospitalization rates. Approximately two-thirds of patients with HF have ischemic etiology, which makes crucial the identification of relevant coronary artery disease (CAD). Moreover, patients with chronic coronary syndrome (CCS) can first show signs of dyspnea and left ventricular (LV) dysfunction. If establishing a diagnosis of HF and consequent management is clear enough, it will not be the same when it comes to recommendations for etiology assessment. Ischemic heart disease is the most studied disease by cardiac multimodality imaging with excellent diagnostic performance. Based on this aspect, the high prevalence of CAD, the worst outcome-HF patients should undergo a diagnostic work-up using these multimodality imaging techniques. The aim of this mini-review is to provide insights on multimodality imaging for diagnosing CCS in patients with new onset of HF and propose a diagnostic work-up based on current international studies and guidelines.

Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer.

BACKGROUND: Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. METHODS: Next-generation sequencing of the whole miRNome and SERS profiling were performed on urine samples collected from 15 patients with BC and 16 control subjects (CTRLs). A retrospective cohort (BC = 66 and CTRL = 50) and RT-qPCR were used to confirm the selected differently expressed miRNAs. Diagnostic accuracy was assessed using machine learning algorithms (logistic regression, naïve Bayes, and random forest), which were trained to discriminate between BC and CTRL, using as input either miRNAs, SERS, or both. The molecular stratification of BC based on miRNA and SERS profiling was performed to discriminate between high-grade and low-grade tumors and between luminal and basal types. RESULTS: Combining SERS data with three differentially expressed miRNAs (miR-34a-5p, miR-205-3p, miR-210-3p) yielded an Area Under the Curve (AUC) of 0.92 ± 0.06 in discriminating between BC and CTRL, an accuracy which was superior either to miRNAs (AUC = 0.84 ± 0.03) or SERS data (AUC = 0.84 ± 0.05) individually. When evaluating the classification accuracy for luminal and basal BC, the combination of miRNAs and SERS profiling averaged an AUC of 0.95 ± 0.03 across the three machine learning algorithms, again better than miRNA (AUC = 0.89 ± 0.04) or SERS (AUC = 0.92 ± 0.05) individually, although SERS alone performed better in terms of classification accuracy. CONCLUSION: miRNA profiling synergizes with SERS profiling for point-of-care diagnostic and molecular stratification of BC. By combining the two liquid biopsy methods, a clinically relevant tool that can aid BC patients is envisaged.

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer.

Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect renal cell carcinoma (RCC), the most prevalent histologic subtype of RC. Thus, serum samples were collected from 23 patients with RCC and 27 controls (CTRL) presenting with a benign urological pathology such as lithiasis or benign prostatic hypertrophy. SERS profiling of deproteinized serum yielded SERS band spectra attributed mainly to purine metabolites, which exhibited higher intensities in the RCC group, and Raman bands of carotenoids, which exhibited lower intensities in the RCC group. Principal component analysis (PCA) of the SERS spectra showed a tendency for the unsupervised clustering of the two groups. Next, three machine learning algorithms (random forest, kNN, naïve Bayes) were implemented as supervised classification algorithms for achieving discrimination between the RCC and CTRL groups, yielding an AUC of 0.78 for random forest, 0.78 for kNN, and 0.76 for naïve Bayes (average AUC 0.77 ± 0.01). The present study highlights the potential of SERS liquid biopsy as a diagnostic and screening strategy for RCC. Further studies involving large cohorts and other urologic malignancies as controls are needed to validate the proposed SERS approach.

Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.

Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore primes interactomes to enhance vulnerability and improve treatment efficacy, enabling therapeutics with traditionally poor performance to become highly efficacious. These findings provide proof-of-principle for a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks.

Bioinspired silk fibroin nano-delivery systems protect against 5-FU induced gastrointestinal mucositis in a mouse model and display antitumor effects on HT-29 colorectal cancer cells in vitro.

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.

The 2021 ultrafast spectroscopic probes of condensed matter roadmap.

In the 60 years since the invention of the laser, the scientific community has developed numerous fields of research based on these bright, coherent light sources, including the areas of imaging, spectroscopy, materials processing and communications. Ultrafast spectroscopy and imaging techniques are at the forefront of research into the light-matter interaction at the shortest times accessible to experiments, ranging from a few attoseconds to nanoseconds. Light pulses provide a crucial probe of the dynamical motion of charges, spins, and atoms on picosecond, femtosecond, and down to attosecond timescales, none of which are accessible even with the fastest electronic devices. Furthermore, strong light pulses can drive materials into unusual phases, with exotic properties. In this roadmap we describe the current state-of-the-art in experimental and theoretical studies of condensed matter using ultrafast probes. In each contribution, the authors also use their extensive knowledge to highlight challenges and predict future trends.

SURGICAL MANAGEMENT OF THE ADRENAL GLAND TUMORS - SINGLE CENTER EXPERIENCE.

CONTEXT: Incidentally discovered solid adrenal tumors must be evaluated from two points of view: the risk of malignancy and the secretory feature. OBJECTIVE: Our aim was to evaluate the surgical technique option in relation with clinical and histopathologic features. DESIGN: We performed a retrospective study that included patients with adrenal gland tumors. SUBJECTS AND METHODS: All patients were operated between 2012 and 2019 by the same surgical team in a single center. RESULTS: The batch included 102 patients with adrenal tumors operated through open surgery (OS, n=41) and laparoscopic surgery (LS, n=61). Tumor localization was especially on the right adrenal gland (n=52, 50.98%). Primary origin of the adrenal gland tumors was in 82 cases (80.39%) and a metastatic origin in 16 cases. Average dimension for surgical resected tumors was 4.02 cm (0.9-12 cm) for the LS group as compared to 7.22 cm (1.3-19 cm) for OS group with a predominant type of surgery represented by adrenalectomy and a conversion rate of 2.94%. The hospital stay was 7.22 days (5-12 days) in the LS group versus 12.72 days (6-57 days) in OS group with significant differences (p<0.01). Also, the postoperative recovery was significantly different (6.5 days versus 2.62 days, p<0.01). CONCLUSION: Laparoscopic approach represents the gold standard in adrenal gland tumors less than five centimeters in size. Adrenalectomy is mostly performed by LS and adenoma is the most frequent histopathologic type, while pheochromocytoma is operated through OS. LS has a significantly reduced hospitalization and postoperative stay compared to OS.

Molecular hydrogen in minerals as a clue to interpret ∂D variations in the mantle.

Trace amounts of water dissolved in minerals affect density, viscosity and melting behaviour of the Earth's mantle and play an important role in global tectonics, magmatism and volatile cycle. Water concentrations and the ratios of hydrogen isotopes in the mantle give insight into these processes, as well as into the origin of terrestrial water. Here we show the presence of molecular H2 in minerals (omphacites) from eclogites from the Kaapvaal and Siberian cratons. These omphacites contain both high amounts of H2 (70 to 460 wt. ppm) and OH. Furthermore, their ∂D values increase with dehydration, suggesting a positive H isotope fractionation factor between minerals and H2-bearing fluid, contrary to what is expected in case of isotopic exchange between minerals and H2O-fluids. The possibility of incorporation of large quantities of H as H2 in nominally anhydrous minerals implies that the storage capacity of H in the mantle may have been underestimated, and sheds new light on H isotope variations in mantle magmas and minerals.

Chaperome Networks - Redundancy and Implications for Cancer Treatment.

The chaperome is a large family of proteins composed of chaperones, co-chaperones and a multitude of other factors. Elegant studies in yeast and other organisms have paved the road to how we currently understand the complex organization of this large family into protein networks. The goal of this chapter is to provide an overview of chaperome networks in cancer cells, with a focus on two cellular states defined by chaperome network organization. One state characterized by chaperome networks working in isolation and with little overlap, contains global chaperome networks resembling those of normal, non-transformed, cells. We propose that in this state, redundancy in chaperome networks results in a tumor type unamenable for single-agent chaperome therapy. The second state comprises chaperome networks interconnected in response to cellular stress, such as MYC hyperactivation. This is a state where no redundant pathways can be deployed, and is a state of vulnerability, amenable for chaperome therapy. We conclude by proposing a change in how we discover and implement chaperome inhibitor strategies, and suggest an approach to chaperome therapy where the properties of chaperome networks, rather than genetics or client proteins, are used in chaperome inhibitor implementation.

Chemical vapor deposition of monolayer-thin WS2 crystals from the WF6 and H2S precursors at low deposition temperature.

Monolayer-thin WS2 with (0002) texture grows by chemical vapor deposition (CVD) from gas-phase precursors WF6 and H2S at a deposition temperature of 450 °C on 300 mm Si wafers covered with an amorphous Al2O3 starting surface. We investigate the growth and nucleation mechanism during the CVD process by analyzing the morphology of the WS2 crystals. The CVD process consists of two distinct growth regimes. During (i) the initial growth regime, a fast and self-limiting reaction of the CVD precursors with the Al2O3 starting surface forms predominantly monolayer-thin WS2 crystals and AlF3 crystals that completely cover the starting surface. During (ii) the steady-state growth regime, a much slower, anisotropic reaction on the bottom, first WS2 layer proceeds with the next WS2 layer growing preferentially in the lateral dimensions. We propose that the precursor adsorption reaction rate strongly diminishes when the precursors have no more access to the Al2O3 surface as soon as the WS2 layer completely covers the Al2O3 surface and that the WS2 crystal basal planes and AlF3 crystals have a low reactivity for WF6 adsorption at 450 °C. Nonetheless, a second layer of WS2 starts to form before the first WS2 layer completely covers the starting surface, albeit the surface coverage of the second layer is low (<20%, after 25 min of CVD reaction). During the steady-state growth regime, predominantly the WS2 crystals in the second monolayer continue to grow in lateral dimensions up to ∼40 nm. These crystals reach larger lateral dimensions compared to the crystals in the bottom, first layer due to low reactivity for WF6 adsorption on the WS2 basal plane compared to Al2O3. Presumably, they grow laterally by precursor species that adsorb on and diffuse across the WS2 surface, before being incorporated at the more reactive edges of the WS2 crystals in the second layer. Such a process proceeds slowly with only up to 40% surface coverage of the second WS2 layer after 150 min of CVD reaction. The CVD reaction is mediated by the starting surface: WF6 precursor preferentially adsorbs on Al2O3, whereas adsorption is not observed on SiO2. Nevertheless, WS2 grows on SiO2 in close proximity to Al2O3 in 90 nm pitch Al2O3/SiO2 line patterns. Hence, functionalization of the starting surface (e.g., SiO2 with Al2O3) can provide opportunities to grow monolayer-thin WS2 crystals at predetermined locations by selective, lateral growth with tunable crystal size, even at low deposition temperatures.

Impact of MoS2 layer transfer on electrostatics of MoS2/SiO2 interface.

Using internal photoemission of electrons from few-monolayer thin MoS2 films into SiO2 we found that the MoS2 layer transfer processing perturbs electroneutrality of the interface, leading to an increase of the electron barrier height by ≈0.5-1 eV as compared to the case of the same films synthesized directly on SiO2. This effect is associated with the formation of an interface dipole, tentatively ascribed to interaction of H2O molecules with the SiO2 surface resulting in the incorporation of silanol (SiOH) groups. This violation of the interface electroneutrality may account for additional electron scattering in ultrathin transferred films and threshold voltage instabilities. Post-transfer annealing in H2S is shown to reduce the transfer-induced interface degradation.

Acute kidney injury: a clinical issue in hospitalized patients with heart failure with mid-range ejection fraction.

INTRODUCTION Acute kidney injury (AKI) during hospitalization is associated with increased mortality in patients with acute heart failure (AHF). In 2016, the European Society of Cardiology introduced the category of heart failure (HF) with mid­range ventricular ejection fraction (HFmrEF) as a distinct category from HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). OBJECTIVES The aim of this study was to evaluate in­hospital mortality risk associated with AKI in patients with AHF, with a focus on the HFmrEF group. PATIENTS AND METHODS A total of 365 health records of patients with a primary diagnosis of acute decompensated heart failure (ADHF) were reviewed. AKI was defined according to Acute Kidney Injury Network criteria. HF was diagnosed based on Framingham criteria. Patients with ADHF were evaluated as 3 separate groups, based on ventricular ejection fraction: HFpEF (≥50%), HFmrEF (40%-49%), and HFrEF (<40%). Risk and survival analyses were conducted on de­identified data. RESULTS The AKI­associated in­hospital mortality odds ratios for HFmrEF and HFrEF groups were 4.55 (95% CI, 1.46-14.18) and 2.59 (95% CI, 1.05-6.41), respectively, with a highly significant difference between the groups (P = 0.002; Mantel-Haenszel test). The hazard ratios in the Cox proportional hazards model were 4.79 (95% CI, 1.54-14.96) and 2.94 (95% CI, 1.27-6.80) for HFmrEF and HFrEF groups, respectively. CONCLUSIONS AKI was associated with a higher risk of mortality in patients with HFmrEF when compared with those with HFrEF, suggesting a stronger prognostic impact of AKI in patients with HFmrEF.

The Clinical Significance of a 'Crazy-Paving' Pattern on Chest Radiology.

A crazy-paving pattern is a non-specific radiological sign which is characterized by the presence of diffuse ground-glass attenuation associated with interlobular septal thickening and intralobular lines. It was initially described as a pathognomonic sign of pulmonary alveolar proteinosis. However, it can be also found in many other diffuse acute and chronic lung diseases including diffuse alveolar haemorrhage (DAH), a rare and life-threatening clinical syndrome which can be caused by many conditions, the most frequent of these being capillaritis associated with systemic autoimmune diseases. In this case report, we describe an 82-year-old female patient with acute respiratory failure and bilateral pulmonary infiltrates with the characteristic crazy-paving pattern. The final diagnosis was isolated DAH induced by microscopic polyangiitis. The patient was treated with IV high dose prednisolone and cyclophosphamide and was mechanically ventilated. Nevertheless, her clinical status progressively deteriorated and she died after 3 days from acute respiratory distress syndrome. LEARNING POINTS: A crazy-paving pattern is a non-specific radiological sign which is characterized by the presence of diffuse ground-glass attenuation associated with interlobular septal thickening.The presence of a crazy-paving pattern together with a progressive fall in haemoglobin levels suggests diffuse alveolar haemorrhage (DAH).A panel for collagen vascular diseases and vasculitis should be immediately performed in patients suspected of having DAH.

Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with Verrucous Carcinoma of the Cervix.

Verrucous carcinoma (VC) is a very rare variant of squamous cell carcinoma of the cervix, difficult to point out in histology because of its benign appearance. We present the case of a 29-year-old woman with a locally advanced cervical VC who underwent radiotherapy followed by radical hysterectomy. After local relapse and despite pelvic exenteration, her condition deteriorated. Treatment of choice in VC is surgery, because of the risk of anaplastic transformation under irradiation, raising the chances of distant spread and converting this rather benign-like type of cancer to an aggressive cancer.

Paramagnetic Intrinsic Defects in Polycrystalline Large-Area 2D MoS2 Films Grown on SiO2 by Mo Sulfurization.

A low-temperature electron spin resonance study has been carried out on large-area high-purity polycrystalline two-dimensional few monolayer (ML) 2H MoS2 films synthesized by sulfurization of Mo layers, with intent to atomically assess mobility-degrading detrimental point defects. This reveals the presence of a distinct previously unreported anisotropic defect of axial symmetry about the c-axis characterized by g // = 2.00145 and g ⊥ = 2.0027, with corresponding density (spin S = ½) ~3 × 1012 cm-2 for a 4 ML thick film. Inverse correlation of the defect density with grain size points to a domain boundary associated defect, inherently incorporated during sample growth. Based on the analysis of ESR signal features in combination with literature data, the signal is tentatively ascribed to the a (di)sulfur antisite defect (S or S2 substituting for a Mo atom). Beset by these defects, the grain boundaries thus emerge as an intolerable threat for the carrier mobility and layer functionality.

Frequency of the UGT1A1*28 Polymorphism in a Romanian Cohort of Gilbert Syndrome Individuals.

BACKGROUND AND AIMS: Gilbert syndrome (GS) is characterized by unconjugated hyperbilirubinemia without liver disease or overt hemolysis and it is found in 3-10% of the general population. Inherited hyperbilirubinaemia is attributable to a reduced UGT1A1 activity. The UGT1A1 promoter (TA) repeats variants are documented of being involved in abnormally elevated bilirubin levels. The aim of the present study is to analyze the impact of UGT1A1 promoter variants on bilirubin levels in Romanian patients clinically supected with GS. METHODS: The study group included 897 subjects: 292 GS patients and 605 healthy controls. Genomic DNA was extracted from the peripheral blood leukocytes. All individuals were screened for the presence of the (TA) insertion in the TATA box region of UGT1A1 gene by PCR amplification. This case-control study was conducted at the Department of Medical Genetics, Synevo, Romania. RESULTS: UGT1A1*28 (7TA) revealed the highest frequency (61.87%) of all individuals, while the UGT1A1*1 (6TA) allele was found in 36.79%. We identified two other variants of the UGT1A1 gene, depending on the number of TA repeats in the promoter: 5TA (0.61%) and 8TA (0.72%). The (TA)7/7 homozygous genotype was identified in 32.33% of all individuals, while the (TA)6/7 heterozygous genotype was the most prevalent (57.64%). The wild type (TA)6/6 was identified in 7.36% of the whole cohort. CONCLUSIONS: Because other polymorphisms have been associated with GS, the absence of the UGT1A1*28 allele does not rule out this condition. The results suggest that in the Romanian population there is a strong correlation between the UGT1A1*28 polymorphism and hyperbilirubinemia in patients with GS.

Nucleation and growth mechanisms of Al2O3 atomic layerdeposition on synthetic polycrystalline MoS2.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs) are of great interest for applications in nano-electronic devices. Their incorporation requires the deposition of nm-thin and continuous high-k dielectric layers on the 2D TMDs. Atomic layer deposition (ALD) of high-k dielectric layers is well established on Si surfaces: the importance of a high nucleation density for rapid layer closure is well known and the nucleation mechanisms have been thoroughly investigated. In contrast, the nucleation of ALD on 2D TMD surfaces is less well understood and a quantitative analysis of the deposition process is lacking. Therefore, in this work, we investigate the growth of Al2O3 (using Al(CH3)3/H2O ALD) on MoS2 whereby we attempt to provide a complete insight into the use of several complementary characterization techniques, including X-ray photo-electron spectroscopy, elastic recoil detection analysis, scanning electron microscopy, and time-of-flight secondary ion mass spectrometry. To reveal the inherent reactivity of MoS2, we exclude the impact of surface contamination from a transfer process by direct Al2O3 deposition on synthetic MoS2 layers obtained by a high temperature sulfurization process. It is shown that Al2O3 ALD on the MoS2 surface is strongly inhibited at temperatures between 125°C and 300°C, with no growth occurring on MoS2 crystal basal planes and selective nucleation only at line defects or grain boundaries at MoS2 top surface. During further deposition, the as-formed Al2O3 nano-ribbons grow in both vertical and lateral directions. Eventually, a continuous Al2O3 film is obtained by lateral growth over the MoS2 crystal basal plane, with the point of layer closure determined by the grain size at the MoS2 top surface and the lateral growth rate. The created Al2O3/MoS2 interface consists mainly of van der Waals interactions. The nucleation is improved by contributions of reversible adsorption on the MoS2 basal planes by using low deposition temperature in combination with short purge times. While this results in a more two-dimensional growth, additional H and C impurities are incorporated in the Al2O3 layers. To conclude, our growth study reveals that the inherent reactivity of the MoS2 basal plane for ALD is extremely low, and this confirms the need for functionalization methods of the TMD surface to enable ALD nucleation.

The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus.

The availability of over-the-counter (OTC) proton pump inhibitors (PPIs) for the short-term (2 weeks) management of frequent heartburn (≥2 days/week) has increased markedly, yet evidence-based recommendations have not been developed. A panel of nine international experts in gastroesophageal reflux disease developed consensus statements regarding the risks and benefits of OTC PPIs using a modified Delphi process. Consensus (based on ≥80% approval) was reached through multiple rounds of remote voting and a final round of live voting. To identify relevant data, the available literature was searched and summarized. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system terminology was used to rate the quality of evidence and strength of recommendations; consensus was based on ≥2/3 agreement. After 4 rounds of review, consensus was achieved for 18 statements. Notably, the available data did not directly reflect OTC use, but instead, prescription use; therefore, extrapolations to the OTC setting were often necessary. This limitation is regrettable, but it justifies performing this exercise to provide evidence-based expert opinion on a widely used class of drugs. The panel determined that using OTC PPIs according to label instructions is unlikely to mask the symptoms of esophageal or gastric cancer or adversely impact the natural history of related precursor conditions. OTC PPIs are not expected to substantially affect micronutrient absorption or bone mineral density or cause community-acquired pneumonia, Clostridium difficile infection, or cardiovascular adverse events. However, OTC PPI use may be associated with slightly increased risks for infectious diarrhea, certain idiosyncratic reactions, and cirrhosis-related spontaneous bacterial peritonitis. The available evidence does not suggest that OTC PPI use consistent with label instructions is associated with substantial health risks. To minimize potential risks, healthcare professionals and consumers must actively participate in decision making when managing reflux-related symptoms in the self-care setting.